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楠原 仙太郎大学院医学研究科 医科学専攻講師
研究活動情報
■ 受賞- 2021年10月 『Ophthalmic Surgery Film Award』 事務局, 2021 Ophthalmic Surgery Film Award (Educational Gold Award), 過熟白内障手術で後悔しないための Visco-Shield technique＋α
- 2018年04月 バイエル薬品株式会社, 第３回バイエル レチナ・アワード, 日本国内の大学、医療機関、研究機関等で眼科医学（網膜領域）に関する研究に携わる45歳未満（2017年4月1日時点）の研究者その他の賞
- Background/Objectives: The object of this study was to determine the outcomes of treatments other than anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) before and after the approval of anti-VEGF therapy in Japan. Methods: This was a retrospective study registered in the database of the Survey of Treatment for DME (STREAT-DME). A total of 1683 patients treated from 2010 to 2017 were included. The patients were divided into two groups: (1) a pre-group, treated before the approval of anti-VEGF agents (2010–2013, n = 771), and (2) a post-group (2014–2017, n = 912). Each group was further categorized based on best-corrected visual acuity (BCVA): (i) improved from poor (>0.3 logMAR units) to good (≤0.3 logMAR units) or (ii) decreased from good to poor. Results: In the pre-group, 18.5% of patients improved from poor to good BCVA out of the total patient population (p < 0.0001), along with 17.3% out of those administered anti-VEGF therapy (p = 0.139), 20.5% of those administered a sub-tenon injection of triamcinolone acetonide (STTA, p = 0.02), 17.7% (p = 0.20) of those administered photocoagulation, and 14.2% of those who underwent pars plana vitrectomy (PPV, p = 0.0001). In the post-group, 21.8% had improved BCVA out of the total patient population (p < 0.0001), along with 27.2% of those undergoing anti-VEGF therapy (p < 0.0001), 16.7% of those administered STTA (p < 0.0001), and 27.2% of those who underwent PPV (p < 0.0001). Conclusions: STTA and PPV are effective to a certain extent, even after the approval of anti-VEGF agents.MDPI AG, 2024年12月, Journal of Clinical Medicine, 13(23) (23), 7336 - 7336研究論文（学術雑誌）
- PURPOSE: To assess the real-world outcome of best-corrected visual acuity (BCVA) following 2-year intervention for treatment-naïve diabetic macular edema (DME) since the approval of anti-vascular endothelial growth factor (VEGF) therapy. METHODS: A total of 1,780 treatment-naïve eyes with DME for which intervention was initiated between 2015 and 2019, and which were followed for 2 years, were extracted from the longitudinal medical records of 37 retinal disease institutions in Japan. Interventions included anti-VEGF therapy, topical corticosteroid therapy, macular photocoagulation, and vitrectomy. The baseline and final BCVA, and the number and timing of interventions were recorded. Eyes were classified according to the year in which intervention was initiated. RESULTS: Over a 2-year period, BCVA improved annually, finally reaching 7 letters. The proportion of eyes in which good vision was maintained (BCVA >20/40) increased to 73.3% in the latest period. The administration of anti-VEGF therapy remained stable, accounting for approximately 90% of eyes. Notably, the proportion of eyes receiving anti-VEGF drugs as first-line treatment increased dramatically to approximately 80%. CONCLUSION: Anti-VEGF therapy has become the first-line treatment since the approval of anti-VEGF drugs for DME. These findings reflect the evolution of DME treatment and highlight the superiority of anti-VEGF therapy and its increased uptake over time.2024年10月, Retina (Philadelphia, Pa.), 英語, 国際誌研究論文（学術雑誌）
- 眼科臨床紀要会, 2024年08月, 眼科臨床紀要, 17(8) (8), 630 - 630, 日本語ステロイドパルス療法後に視機能改善を認めた自己免疫網膜症疑いの1例
- 眼科臨床紀要会, 2024年08月, 眼科臨床紀要, 17(8) (8), 631 - 631, 日本語癌関連網膜症疑いを契機に乳癌の診断に至った1例
- AIMS/INTRODUCTION: To conduct a multicenter survey of visually impaired patients with diabetes mellitus (DM) and to identify the physical and ocular characteristics that lead to blindness in Japan. MATERIALS AND METHODS: Visually impaired patients with diabetes mellitus in Japan were divided into blind and low-vision groups according to the World Health Organization classification. Data on parameters related to diabetes mellitus and ocular complications in the right and left eyes were collected from 19 highly advanced medical facilities and compared between the two groups. RESULTS: Among 408 visually impaired persons (blind group: 257, low-vision group: 151), 72.1% were under 70 years of age. The rates of neovascular glaucoma (NVG) (right eye, P = 0.041; left eye, P = 0.0031) or proliferative diabetic retinopathy (PDR) (right eye: P = 0.014, left eye: P = 0.0047) and the rate of proliferative membrane beyond half of the retinal area (right eye: P = 0.0263, left eye: P = 0.037) were significantly higher in the blind group. The direct cause of visual impairment was retinal atrophy, common in both groups. Neovascular glaucoma and diabetic macular edema were equally prevalent in the blind and low-vision groups, respectively. CONCLUSIONS: In Japan, blind patients with diabetes mellitus are characterized by severe conditions such as neovascular glaucoma and progressive proliferative diabetic retinopathy upon their initial visit to an advanced care facility. These results highlight the importance of monitoring retinopathy through regular ophthalmological examinations, internal medicine, and appropriate therapeutic intervention.2024年03月, Journal of diabetes investigation, 英語, 国内誌研究論文（学術雑誌）
- (公財)日本眼科学会, 2024年03月, 日本眼科学会雑誌, 128(3) (3), 234 - 255, 日本語
- (公財)日本眼科学会, 2024年03月, 日本眼科学会雑誌, 128(臨増) (臨増), 174 - 174, 日本語高濃度フィブリノーゲンによるICAM-1経路を介した網膜組織傷害の検討
- (公財)日本眼科学会, 2024年03月, 日本眼科学会雑誌, 128(臨増) (臨増), 208 - 208, 日本語若年性慢性虹彩毛様体炎の臨床像の検討
- To investigate the association between lactate metabolism and glaucoma, we conducted a multi-institutional cross-sectional clinical study and a retinal metabolomic analysis of mice with elevated intraocular pressure (IOP) induced by intracameral microbead injection. We compared lactate concentrations in serum and aqueous humor in age-matched 64 patients each with primary open-angle glaucoma (POAG) and cataract. Neither serum nor aqueous humor lactate concentrations differed between the two groups. Multiple regression analysis revealed that only body mass index showed a significant positive correlation with serum and aqueous humor lactate concentration in POAG patients (rs = 0.376, P = 0.002, and rs = 0.333, P = 0.007, respectively), but not in cataract patients. L-Lactic acid was one of the most abundantly detected metabolites in mouse retinas with gas chromatography and mass spectrometry, but there were no significant differences among control, 2-week, and 4-week IOP elevation groups. After 4 weeks of elevated IOP, D-glucose and L-glutamic acid ranked as the top two for a change in raised concentration, roughly sevenfold and threefold, respectively (ANOVA, P = 0.004; Tukey-Kramer, P < 0.05). Glaucoma may disrupt the systemic and intraocular lactate metabolic homeostasis, with a compensatory rise in glucose and glutamate in the retina.2024年02月, Scientific reports, 14(1) (1), 3683 - 3683, 英語, 国際誌研究論文（学術雑誌）
- This study investigated aniseikonia after reduced-fluence photodynamic therapy (RFPDT) for central serous chorioretinopathy (CSC). We examined 48 eyes of 48 patients (38 men; mean age, 49.2 ± 9.9 years) with CSC resolved after RFPDT. Horizontal and vertical aniseikonia were measured using the New Aniseikonia Test at baseline, 6 months, and 12 months after RFPDT. The maximum absolute value of the horizontal and vertical measurements indicated the aniseikonia score. The aniseikonia score was 2.2 ± 2.3 at 6 months and 2.2 ± 2.0 at 12 months after RFPDT, both of which improved significantly from the baseline score of 4.1 ± 2.9 (P < 0.05 and P < 0.01, respectively). The 12-month aniseikonia score significantly correlated with the baseline aniseikonia score (P = 0.047), outer nuclear thickness at baseline (P = 0.027) and 12 months after RFPDT (P = 0.014), baseline SRD area (P = 0.005), and ellipsoid zone disruption at 12 months after RFPDT (P = 0.021). In multivariate analysis, baseline serous retinal detachment (SRD) area (P = 0.034) was significantly associated with aniseikonia score at 12 months after RFPDT. Eyes with a larger SRD area might have higher aniseikonia scores even after SRD resolution following RFPDT.2023年10月, Scientific reports, 13(1) (1), 17133 - 17133, 英語, 国際誌研究論文（学術雑誌）
- PURPOSE: We have previously demonstrated that prolonged use of glaucoma medications was associated with a poor surgical outcome of ab interno trabeculotomy (µTLO). Given that almost all types of glaucoma eye drop either enhance the drainage through the uveoscleral pathway or reduce aqueous humor production, we hypothesized that prolonged use of these medications might cause disuse atrophy of the conventional pathway. In contrast, ripasudil increases the conventional outflow and eventually shows a favorable outcome of µTLO. This study aimed to evaluate the effect of ripasudil use on µTLO outcomes. METHOD: The medical charts of 218 patients who underwent µTLO were analyzed retrospectively. We compared the 1-year outcome between ripasudil users versus nonusers by using propensity score matching. We set the covariates as age, sex, glaucoma types, preoperative intraocular pressure (IOP), the mean deviation values of visual field tests, the presence or absence of concomitant cataract surgery, trabecular meshwork incision range, the presence or absence of any glaucoma medication except ripasudil and duration of glaucoma medical therapy. Success was defined as a postoperative IOP between 5 and 21 mmHg, a ≥ 20% IOP reduction from baseline, and no additional glaucoma surgery at postoperative 1 year. RESULT: Fifty-seven patients each were allocated to the ripasudil users or nonusers. The 1-year success rates were 74% in ripasudil users and 51% in nonusers (p = 0.01). Kaplan‒Meier survival curves also showed that the ripasudil users had a higher survival distribution (p = 0.01). CONCLUSION: The patients who took ripasudil showed a favorable 1-year outcome of µTLO.2023年09月, Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 261(9) (9), 2603 - 2610, 英語, 国際誌研究論文（学術雑誌）
- To evaluate the functional and anatomical effects of switching to faricimab for patients with neovascular age-related macular degeneration (nAMD) refractory to intravitreal aflibercept, this retrospective study evaluated patients with nAMD who received intravitreal injections of aflibercept (IVA) every <8 weeks and were switched to faricimab. After switching, the patients were treated with a treatment and extended regimen that started with the interval just before switching and received at least three injections. We evaluated changes in the best-corrected visual acuity (BCVA), central retinal thickness (CRT), central choroidal thickness (CCT), treatment interval, and presence of retinal fluid. Overall, 55 eyes from 55 patients were examined. After three injections of faricimab, the BCVA and CCT did not change significantly. However, the CRT decreased significantly (p < 0.05), the injection interval was significantly extended (7.5 ± 2.3 vs. 5.9 ± 1.5 weeks, p < 0.01), and the rates of the presence of intraretinal fluid and subretinal fluid decreased significantly to 16.4% and 40% of eyes, respectively (both p < 0.01). An ocular adverse event (retinal pigment epithelium tear) developed in one eye. Switching to faricimab was effective for anatomic changes. It may be an additional treatment option for some eyes refractory to IVA.2023年08月, Journal of clinical medicine, 12(15) (15), 英語, 国際誌研究論文（学術雑誌）
- To report the usefulness of intraoperative real-time adjustment of intraocular lens (IOL) tilt during the intrascleral fixation with intraoperative optical coherence tomography (iOCT) as a clinical evaluation and investigate the factors contributing to IOL tilt using iOCT as an experimental evaluation. Retrospective cohort study and experimental research. As a clinical evaluation, the medical records of 43 eyes of 41 patients who underwent intrascleral IOL fixation combined with real-time iOCT observation were retrospectively reviewed. As an experimental evaluation, in order to investigate the factors contributing to IOL tilt, the four experiments were performed using iOCT. The mean IOL tilt angle (°) at the end of surgery and 3 months after surgery were 1.81 ± 1.15 and 2.10 ± 1.66, respectively (p = 0.46). No apparent intra- or postoperative complications occurred during the follow-up period. The experimental evaluation indicated that the IOL tilt was influenced by the insertion angle of the haptic in the vertical direction. The mean IOL tilt angle (°) was 1.94 ± 0.09, 4.67 ± 0.11, 8.90 ± 0.11, and 15.78 ± 0.85 when the insertion angle of the haptic was 0°, 10°, 27.5°, and 45° in the vertical direction, respectively (p < 0.01). Clinical and experimental IOL tilt assessment using iOCT is interactively useful for better quality surgery and better postoperative outcome.2023年07月, Scientific reports, 13(1) (1), 12065 - 12065, 英語, 国際誌研究論文（学術雑誌）
- The appropriate surgical technique to improve the closure rate of perioperative full-thickness macular hole (FTMH) secondary to submacular hemorrhage (SMH) with sub-internal limiting membrane (ILM) hemorrhage caused by retinal arterial macroaneurysm (RAM) rupture remains an unsolved clinical problem. Several ILM transplantation techniques have been attempted, but these are challenging. Our new technique can remove sub-ILM hemorrhage with the central fovea ILM intact, without peeling the ILM. The medical records of three eyes from three patients with SMH and sub-ILM hemorrhage secondary to RAM rupture were retrospectively reviewed. During the surgery, a small ILM fissure was made outside the central fovea with ILM forceps, and sub-ILM hemorrhage was washed out through it by manually spraying balanced salt solution. Sub-ILM hemorrhage removal was achieved successfully in all eyes, with no occurrences of FTMH or other complications. Best-corrected decimal visual acuity improved from 0.05 (Snellen equivalent (SE), 20/400), 0.05 (SE, 20/400), and 0.05 (SE, 20/400) preoperatively to 0.3 (SE, 20/63), 0.4 (SE, 20/50), and 0.15 (SE, 20/125) at 3 months postoperatively, respectively. This new technique may help keep the foveal ILM intact and prevent perioperative FTMH formation.2023年05月, Journal of clinical medicine, 12(9) (9), 英語, 国際誌研究論文（学術雑誌）
- PURPOSE: The aim of this study is to explore the clinical features and associated factors of intraocular inflammation (IOI) following intravitreal brolucizumab (IVBr) administration for neovascular age-related macular degeneration (nAMD). METHODS: This retrospective study included 87 eyes from 87 Japanese patients with nAMD who were followed up for 5 months after the initial administration of IVBr as switching therapy. Clinical pictures of IOI post-IVBr and changes in best corrected visual acuity (BCVA) at 5 months were evaluated between eyes with and without IOI (non-IOI). The association between IOI and baseline factors (age, sex, BCVA, hypertension, and/or arteriosclerotic changes in the fundus, subretinal hyperreflective material [SHRM], and macular atrophy) was evaluated. RESULTS: Of the 87 eyes, 18 (20.6%) developed IOI and 2 (2.3%) developed retinal artery occlusion. There were 9 (50%) cases of posterior or pan-uveitis among eyes with IOI. The mean interval from initial IVBr administration to IOI was 2 months. The mean changes in logMAR BCVA at 5 months were significantly worse in IOI eyes than in non-IOI eyes (0.09 ± 0.22 vs. - 0.01 ± 0.15, P = 0.03). There were 8 (44.4%) and 7 (10.1%) cases of macular atrophy and 11 (61.1%) and 13 (18.8%) cases of SHRM in the IOI and non-IOI groups, respectively. SHRM and macular atrophy were significantly associated with IOI (P = 0.0008 and P = 0.002, respectively). CONCLUSION: In IVBr therapy for nAMD, eyes with SHRM and/or macular atrophy should be observed more meticulously, given the increased risk of developing IOI, which is associated with insufficient BCVA gain.2023年03月, Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 261(8) (8), 2359 - 2366, 英語, 国際誌研究論文（学術雑誌）
- Background and Objectives: Faricimab is a novel bispecific antibody with Fab regions inhibiting both vascular endothelial growth factor-A and angiopoietin-2. Therefore, this study aimed to obtain short-term outcomes of intravitreal injection of faricimab (IVF) for the treatment of diabetic macular edema (DME) in daily clinical practice. Materials and Methods: A retrospective review was carried out on consecutive patients with DME who had been treated with IVF and were followed up for at least 1 month. Outcome measures included changes in logMAR best-corrected visual acuity (logMAR BCVA), central retinal thickness (CRT), number of IVF administrations, and safety. Clinical outcomes were also compared between the treatment-naïve and switch groups. Results: A total of 21 consecutive DME eyes from 19 patients were identified. The mean number of IVFs was 1.6 ± 0.8 during the mean follow-up time of 5.5 months. The overall mean logMAR BCVA following IVF was 0.236, 0.204, 0.190, and 0.224 at baseline, 1, 3, and 6 months, respectively, without a significant change from baseline to 1 month (p = 0.176) or for 6 months (p = 0.923). The overall mean CRT (μm) following IVF was 400.6, 346.6, 342.1, and 327.5 at baseline, 1, 3, and 6 months, respectively. CRT significantly decreased from baseline to 1 month (p = 0.001) but did not reach a significant level over 6 months following IVF (p = 0.070). No significant difference in BCVA or CRT was observed between the treatment-naïve and switch groups. No serious safety concerns were noted. Conclusions: IVF for the treatment of DME may preserve visual acuity and improve macular thickness without serious safety concerns in the short term in a real-world clinical setting.2023年03月, Medicina (Kaunas, Lithuania), 59(4) (4), 英語, 国際誌研究論文（学術雑誌）
- (公財)日本眼科学会, 2023年03月, 日本眼科学会雑誌, 127(臨増) (臨増), 270 - 270, 日本語日本におけるフックス虹彩毛様体炎症候群の低い有病率の原因についての検討
- PURPOSE: We investigated potential risk factors for visual prognosis in Japanese patients with exogenous endophthalmitis. METHODS: In this retrospective observational multicenter cohort study, risk factors for legal blindness at 12 weeks after treatment initiation were evaluated based on patient characteristics, initial BCVA, causative events, pathogens, ocular symptoms, duration from symptom onset to initial treatment, and selected treatments. RESULTS: Overall, 23.1% of eyes developed legal blindness. The six risk factors for legal blindness were presence of eye pain, pathogen identification, poor BCVA at the initial visit, longer duration from symptom onset to initial treatment, type of causative event, and type of causative pathogen. Regarding the type of causative pathogen, coagulase-negative staphylococci was associated with a better visual impairment outcome. CONCLUSION: Exogenous endophthalmitis remains a severe ocular infection; however, it can be managed with rapid treatment, as well as other advances in medical knowledge and technology.2023年01月, Ocular immunology and inflammation, 1 - 9, 英語, 国際誌研究論文（学術雑誌）
- PURPOSE: To compare the two-year outcome of half-time photodynamic therapy (htPDT) in chronic central serous chorioretinopathy (cCSC) with and without choroidal neovascularization (CNV). METHODS: In this retrospective study, we included 88 eyes of 88 patients with cCSC who underwent htPDT and were followed up for more than 24 months. Patients were divided into two groups with (21 eyes) or without (67 eyes) CNV before htPDT treatment. The best-corrected visual acuity (BCVA), central retinal thickness (CRT), subfoveal choroidal thickness (SCT), and the presence of subretinal fluid (SRF) were evaluated at baseline and at 1, 3, 6, 12, and 24 months after PDT. RESULTS: A significant intergroup difference was noted in terms of age (P = 0.038). Significant improvements in the BCVA and SCT were found at all time points in eyes without CNV but only at 24 months in eyes with CNV. CRT was significantly reduced in both groups at all time points. No significant intergroup differences were noted in terms of BCVA, SCT and CRT at all time points. There were significant differences in the rate of recurrent and persistent SRF between groups (22.4% (without CNV) vs. 52.4% (with CNV), P = 0.013, and 26.9% (without CNV) vs. 57.1% (with CNV), P = 0.017, respectively). The presence of CNV was significantly associated with the recurrence and persistence of SRF after initial PDT (P = 0.007 and 0.028, respectively). Logistic regression analyses showed that the baseline BCVA, and not the presence of CNV, was significantly associated with BCVA at 24 months after initial PDT (P < 0.01). CONCLUSIONS: A htPDT for cCSC was less effective in eyes with CNV than in those without CNV regarding the recurrence and persistence of SRF. Additional treatment might be required in eyes with CNV during 24-month follow-up periods.2023年, PloS one, 18(5) (5), e0284979, 英語, 国際誌研究論文（学術雑誌）
- PURPOSE: To report the usefulness of a new surgical method using intraoperative optical coherence tomography that can more accurately place the buckling material for scleral buckling using a noncontact wide-angle viewing system with a cannula-based chandelier endoilluminator for the treatment of rhegmatogenous retinal detachment. METHODS: The medical records of 12 eyes of 11 patients with rhegmatogenous retinal detachment treated with scleral buckling combined with real-time intraoperative optical coherence tomography observation were retrospectively reviewed. RESULTS: Real-time observations of the positional relationship between the protrusion of buckling material and retinal breaks with intraoperative optical coherence tomography revealed that retinal breaks were not properly placed on the protrusion of the buckling material in five eyes, requiring the intraoperative repositioning of the buckling material. Eventually, the scleral buckling combined with real-time intraoperative optical coherence tomography observation yielded the initial anatomical success rates of 100% without noteworthy intraoperative or postoperative complications. CONCLUSION: This procedure is a novel approach that enables safer and more accurate placement of the buckling material and may contribute to improving the outcomes of scleral buckling in the future.2022年12月, Retina (Philadelphia, Pa.), 42(12) (12), 2395 - 2400, 英語, 国際誌研究論文（学術雑誌）
- PURPOSE: To report the characteristics of a case series of ocular inflammatory events following COVID-19 vaccination in Japan. STUDY DESIGN: Retrospective multicenter study METHODS: In this retrospective multicenter survey, a questionnaire was sent to 16 Japanese hospitals that had uveitis specialty clinics. Information on patients who developed ocular inflammatory events within 14 days of COVID-19 vaccination between February 2021 and December 2021 was collected. RESULTS: Thirty-seven patients were diagnosed with ocular inflammatory events following COVID-19 vaccination. The mean age was 53.4 ± 16.4 years (range, 26-86 years), and the mean time to onset after vaccination was 6.3 ± 4.2 days (range, 1-14 days). Vogt-Koyanagi-Harada disease (VKH) was the most common event (n = 17 patients, 46%), followed by anterior uveitis (n = 6), infectious uveitis (n = 3), acute zonal occult outer retinopathy (AZOOR) (n = 2), sarcoidosis-associated uveitis (n = 1), acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 1), optic neuritis (n = 1), multiple evanescent white dot syndrome (MEWDS) (n = 1), Posner-Schlossman syndrome (n = 1), and unclassified uveitis (n = 4). Twenty-eight cases occurred after BNT162b2 vaccination (Pfizer-BioNTech) and 8 after mRNA-1273 vaccination (Moderna), whilst 1 patient had no information about vaccine type. CONCLUSIONS: COVID-19 vaccination can be related to various types of ocular inflammatory events. When we encounter patients with ocular inflammatory disease, we should consider that it may be an adverse effect of COVID-19 vaccination.2022年11月, Japanese journal of ophthalmology, 67(1) (1), 1 - 8, 英語, 国内誌研究論文（学術雑誌）
- Anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) improves visual acuity. However, repeated injections during routine outpatient visits are required to maintain this effect. The recent sudden global outbreak of coronavirus disease 2019 (COVID-19) had a major impact on daily life, including medical care, such as the provision of VEGF therapy. We retrospectively investigated the relationship between the number of anti-VEGF injections for DME and the number of new COVID-19-positive patients at 23 centers in Japan. We also surveyed ophthalmologists regarding the impact of the COVID-19 pandemic on anti-VEGF therapy. In the third and fourth waves of the pandemic, when the number of infected patients increased, the number of injections significantly decreased. In the first, third, and fourth waves, the number of injections increased significantly during the last month of each wave. Approximately 60.9% of ophthalmologists reported that the number of injections decreased after the pandemic. Of the facilities, 52.2% extended the clinic visit intervals; however, there was no significant difference in the actual number of injections given between before and after the pandemic. Although the number of injections temporarily decreased, Japanese ophthalmologists maintained the total annual number of anti-VEGF injections for DME during the pandemic.2022年11月, Journal of clinical medicine, 11(22) (22), 英語, 国際誌研究論文（学術雑誌）
- 眼科臨床紀要会, 2022年11月, 眼科臨床紀要, 15(11) (11), 762 - 763, 日本語黄斑下出血に対する組織プラスミノーゲン活性化因子併用硝子体内ガス注入の治療成績
- 眼科臨床紀要会, 2022年10月, 眼科臨床紀要, 15(10) (10), 688 - 688, 日本語ブロルシズマブ硝子体内注射後の眼内炎症の頻度と特徴
- PURPOSE: We investigated potential predictive factors for visual prognosis in Japanese patients with endogenous endophthalmitis. DESIGN: Retrospective observational multicenter cohort study. METHODS: We examined the characteristics of 77 Japanese patients with endogenous endophthalmitis and performed statistical analyses of these real-world data. The primary endpoint was the identification of factors associated with visual prognosis. We examined differences between patients in the better vision and legal blindness groups at 12 weeks after treatment initiation. RESULTS: The five risk factors for visual impairment at 12 weeks after treatment initiation were presence of pressure injuries, severe clinical symptoms (presence of eye pain and ciliary injection), pathogen identification, and poor best-corrected visual acuity at baseline. Staphylococcus aureus and fungus were associated with a better visual impairment outcome. CONCLUSIONS: Endogenous endophthalmitis remains a severe ocular infection; however, it can be managed with rapid treatments, as well as other advances in medical knowledge and technology.2022年08月, Ocular immunology and inflammation, 1 - 8, 英語, 国際誌研究論文（学術雑誌）
- PURPOSE: We investigated efficacy and safety of adalimumab (ADA) treatment for exacerbation or recurrence of Vogt-Koyanagi-Harada (VKH) patients. METHODS: Medical records of 70 VKH patients who received ADA treatment for more than 6 months were retrospectively investigated. RESULTS: The mean age of VKH patients was 54.8 ± 15.1 years, and male/female ratio was 34/36, and sunset glow fundus was observed in 71.4%. Subfoveal choroidal thickness, indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment for 6 months compared to baseline, while LogMAR and flare counts were also improved without being statistically significant. Adverse events were observed in 17.1%, in which tuberculosis was at 7.14% and psoriasis was at 2.86%; however, ADA treatment was continued in 91.4%. CONCLUSIONS: ADA was shown to be effective to achieve remission of VKH disease refractory to conventional treatments and was generally well tolerated with few serious adverse events.2022年06月, Ocular immunology and inflammation, 1 - 9, 英語, 国際誌研究論文（学術雑誌）
- PURPOSE: To describe angiographic features of a case of delayed-onset retinal vascular occlusion and intraocular inflammation (IOI) following brolucizumab intravitreal injection (IVI). OBSERVATIONS: A 75-year-old woman with advanced age-related macular degeneration (AMD) complained of persistent distorted vision despite 1 aflibercept 2-mg IVI and subsequent 1 brolucizumab 6-mg IVI. At 20 days after brolucizumab IVI, clinical examination showed no signs of IOI, her right best-corrected visual acuity (BCVA) was 1.0 (Snellen equivalent, 20/20). Simultaneous fluorescein and indocyanine green angiography (FA/IA) performed 2 days later showed no abnormalities, but she noticed floaters and decreased vision in her right eye 5-6 hours after FA/IA. At 44 days after brolucizumab IVI, her right BCVA was 0.6 (Snellen equivalent, 20/33), and clinical examination revealed mutton-fat keratic precipitates, anterior chamber cells (2+), vitreous cells, vitreous haze (1+), and sheathed retinal vessels. FA showed filling defect and vascular staining/leakage at several retinal arteries and dye leakage from optic disc edge, where IA demonstrated dye staining as well. However, there was a retinal artery occlusion site which lacks angiographic signs indicative of active retinal vasculitis. The patient was diagnosed with retinal vascular occlusion and IOI which occurred approximately 3 weeks after brolucizumab IVI. CONCLUSIONS AND IMPORTANCE: Delayed brolucizumab-associated retinal vascular occlusion and IOI can develop from a condition in which no apparent abnormal findings exist on FA/IA. Together with the fact that angiographic signs observed in this case were not severe enough to induce retinal artery occlusion, potent and prolonged vascular endothelial growth factor inhibition by brolucizumab IVI might have caused severe damage to retinal vascular endothelial cells. Then, the damage subsequently led to retinal vascular occlusions and enhanced immune reaction to brolucizumab. The latter would be enhanced through the migration of immune cells towards vitreous cavity being allowed by disrupted inner blood retinal barrier.2022年06月, American journal of ophthalmology case reports, 26, 101521 - 101521, 英語, 国際誌
- AIMS/INTRODUCTION: In older patients, the management of diabetic macular edema (DME) can be complicated by comorbidities, geriatric syndrome, and socioeconomic status. This study aims to evaluate the effects of aging on the management of DME. MATERIALS AND METHODS: This is a real-world clinical study including 1,552 patients with treatment-naïve center-involved DME. The patients were categorized into 4 categories by age at baseline (C1, <55; C2, 55-64; C3, 65-74; and C4, ≥75 years). The outcomes were the change in logarithm of the minimum angle of resolution best-corrected visual acuity (logMAR BCVA) and central retinal thickness (CRT), and the number of treatments from baseline to 2 years. RESULTS: From baseline to 2 years, the mean changes in logMAR BCVA from baseline to 2 years were -0.01 in C1, -0.06 in C2, -0.07 in C3, and 0.01 in C4 (P = 0.016), and the mean changes in CRT were -136.2 μm in C1, -108.8 μm in C2, -100.6 μm in C3, and -89.5 μm in C4 (P = 0.008). Treatments applied in the 2 year period exhibited decreasing trends with increasing age category on the number of intravitreal injections of anti-VEGF agents (P = 0.06), selecting local corticosteroid injection (P = 0.031), vitrectomy (P < 0.001), and laser photocoagulation outside the great vascular arcade (P < 0.001). CONCLUSIONS: Compared with younger patients with DME, patients with DME aged ≥75 years showed less frequent treatment, a lower BCVA gain, and a smaller CRT decrease. The management and visual outcome in older patients with DME would be unsatisfactory in real-world clinical practice.2022年04月, Journal of diabetes investigation, 13(8) (8), 1339 - 1346, 英語, 国内誌研究論文（学術雑誌）
- (公財)日本眼科学会, 2022年03月, 日本眼科学会雑誌, 126(臨増) (臨増), 213 - 213, 日本語加齢黄斑変性に対するブロルシズマブ投与後の眼内炎症の臨床像と関連事前因子の検討
- (公財)日本眼科学会, 2022年03月, 日本眼科学会雑誌, 126(臨増) (臨増), 274 - 274, 日本語脈絡膜新生血管の有無による慢性中心性脈絡網膜症患者における治療成績
- (公財)日本眼科学会, 2022年03月, 日本眼科学会雑誌, 126(臨増) (臨増), 276 - 276, 日本語滲出型加齢黄斑変性に対するブロルシズマブへの切り替え効果についての検討
- PURPOSE: Non-infectious uveitis associated with Vogt-Koyanagi-Harada (VKH) disease or sarcoidosis is commonly treated with systemic corticosteroids (SCS). We assessed the use of SCS for non-infectious uveitis relapses in Japanese clinical practice. STUDY DESIGN: Multicenter, retrospective chart review (UMIN Clinical Trial Registry; UMIN000032390). METHODS: One hundred fifty-seven patients (15- ≤ 75 years; 103 VKH disease, 54 sarcoidosis) given SCS to treat a relapse of non-infectious intermediate, posterior, or panuveitis accompanying VKH disease or sarcoidosis were studied (August 2011-December 2018). SCS dose and duration, concomitant medications, subsequent relapses, and steroid-related adverse drug reactions (ADRs) were analyzed for 12 months after target relapse treatment. Relationships between background factors and total SCS dose were analyzed (logistic regression). RESULTS: Mean (± SD) total SCS dose over 12 months after target relapse treatment was 3874 ± 2775 mg, and was higher in patients with immunosuppressants than in those without (4575 mg vs 3496 mg). Immunosuppressant use was the only factor significantly associated with higher total SCS dose (p = 0.0196). Mean duration of SCS treatment for relapse was 318.7 ± 89.3 days. Only 29.3% of patients were steroid-free after 12 months; the percentage was higher in patients without immunosuppressants (36.3% vs 16.4%). Subsequent relapse was experienced by 39.5% of patients, and 13.4% had a steroid-related ADR (mostly glaucoma or diabetes). CONCLUSION: In Japanese clinical practice, many patients with recurrent uveitis accompanying VKH disease or sarcoidosis received SCS for relapse for ≥ 300 days, suggesting that reducing corticosteroids is challenging in patients with difficulty suppressing inflammation.2022年03月, Japanese journal of ophthalmology, 66(2) (2), 130 - 141, 英語, 国内誌研究論文（学術雑誌）
- PURPOSE: We investigated the efficacy and safety of adalimumab (ADA) treatment for chronic recurrent Vogt-Koyanagi-Harada (VKH) patients with sunset glow fundus (SGF). METHODS: Medical records of 50 chronic recurrent VKH patients with SGF who received ADA treatment for more than 6 months were retrospectively reviewed. RESULTS: The mean age of chronic recurrent VKH patients with SGF was 55.9 ± 14.4 years, and the male/female ratio was 26/24. Before ADA treatment, the mean daily dose of systemic corticosteroids was 16.5 ± 12.7 mg, and 22 patients (44%) were under immunosuppressors. LogMAR visual acuity (VA), flare counts, subfoveal choroidal thickness (SFCT), indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment at 6 months compared to baseline. Among all parameters, flare count was significantly related to LogMAR VA. LogMAR VA was significantly related to flare counts but not to SFCT nor to ICGA scores. ADA treatment was continued in 94%. CONCLUSION: ADA was shown to be effective in achieving remission of chronic recurrent VKH disease with SGF refractory to conventional treatments, and was generally well tolerated with few serious adverse events.2022年, Saudi journal of ophthalmology : official journal of the Saudi Ophthalmological Society, 36(4) (4), 380 - 386, 英語, 国際誌研究論文（学術雑誌）
- PURPOSE: To evaluate the clinical characteristics, treatment trends, and visual prognosis of submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD) and retinal arterial macroaneurysm (RAM). METHODS: This retrospective study enrolled 187 Japanese patients with SMH at 10 institutions from 2015 to 2018. Medical records including SMH etiology, best-corrected visual acuity (BCVA), fundus photographs, optical coherence tomography images, and selected treatments were analyzed. RESULTS: Major causes of SMH were typical nAMD (tnAMD) (18%), polypoidal choroidal vasculopathy (PCV) (50%) and RAM (29%). Age, male/female ratio, baseline BCVA, central retinal thickness, and involved retinal layers were significantly different between etiologies (all P<0.0001). Treatment with anti-vascular endothelial growth factor drugs with and without intravitreal gas injection was chosen for half of eyes in the tnAMD and PCV groups, whereas vitrectomy was performed in 83.7% of eyes with RAM. The final BCVA improved significantly from baseline in the PCV and RAM groups (P = 0.0009, P<0.0001) and final BCVA was significantly better in the PCV group at a level similar to the other groups (P = 0.0007, P = 0.0008). BCVA improvement from baseline was significantly greater in the RAM group compared with the tnAMD (P = 0.0152) and PCV (P = 0.017) groups. Multivariate analysis revealed better final BCVA was significantly associated with younger age (P = 0.0054), better baseline BCVA (P = 0.0021), RAM subtype (P = 0.0446), and no tnAMD (P = 0.001). CONCLUSIONS: The characteristics of, and treatment strategy for, SMH were different between the underlying diseases. Anti-vascular endothelial growth factor treatment with or without expansile gas was mainly chosen for SMH in tnAMD and PCV, whereas vitrectomy with gas was the most common treatment for RAM, and the higher rate for vitrectomy might result in the greater BCVA improvement in the RAM group than in the other groups. Final BCVA was better in PCV, RAM, and tnAMD, in that order, because patients with PCV were younger and had better baseline BCVA.2022年, PloS one, 17(9) (9), e0274508, 英語, 国際誌研究論文（学術雑誌）
- AIM: To investigate the causes of low prevalence of Fuchs' uveitis syndrome (FUS) in Japan. METHODS: Medical records of 160 patients diagnosed with FUS at 14 uveitis specialty facilities in Japan were reviewed retrospectively. RESULTS: In 160 FUS patients, mean follow-up period before referral to our uveitis facilities was 31.6 ± 50.9 months. The most common reason for referral was idiopathic uveitis (61.9%), followed by cataract (25.0%), high intraocular pressure (IOP) including glaucoma (16.3%), and FUS (14.4%). Unilateral involvement was 96.9%. The most frequent ocular finding of FUS was anterior inflammation (91.9%), followed by stellate-shaped keratic precipitates (88.1%), cataract/pseudophakia (88.1%), diffuse iris atrophy (84.4%), vitreous opacity (62.5%), heterochromia (53.1%) and high IOP including glaucoma (36.3%). As treatments of these ocular findings, cataract surgery was performed in 52.5%, glaucoma surgery in 10.6%, and vitrectomy in 13.8%. Mean logMAR VA was 0.28 ± 0.59 at the initial visit, and decreased significantly to 0.04 ± 0.32 at the last visit. Proportions of FUS patients with BCVA <0.1 and 0.1 to <0.5 decreased, while that of ≥0.5 increased at the last visit compared with the initial visit. CONCLUSIONS: Ocular findings of FUS in Japanese FUS patients were consistent with the characteristic features. The low prevalence of FUS in Japan may be a result of being overlooked and misdiagnosed as mild idiopathic uveitis, cataract, and/or glaucoma.2022年, Frontiers in medicine, 9, 999804 - 999804, 英語, 国際誌研究論文（学術雑誌）
- The aim of this study was to determine the prevalence and progression of diabetic retinopathy (DR) with hyperglycemic disorders during pregnancy (HDPs) in Japan between 2013 and 2018 using two cohorts. The patients with HDPs were classified as those with pre-existing DM (pexD), gestational DM (GDM), and overt DM (ODM). Cohort 1 was obtained from the health claims database whose diseases were classified by the International Classification of Diseases-10. Cohort 2 was derived from a retrospective, multicenter analysis of the medical records of 225 patients from 10 ophthalmological institutions. In Cohort 1, there were 5268 patients with an HDP prevalence of 8.4%. Among them, 73 of 1139 patients had pexD (6.4%) and 61 of 4129 patients with GDM (1.5%) had DR; the overall prevalence of DR was 2.5%. In Cohort 2, 36 of 225 patients (16.0%) had DR, and 149 patients were followed at the early and late stages of pregnancy. Moreover, 10 of the 102 patients with pexD (9.8%) and two of five patients with ODM (40.0%) had a progression of DR. In conclusion, the prevalence and progression of DR in patients with pexD is lower than previously reported. More attention should be given to pexD and ODM.2021年12月, Journal of clinical medicine, 11(1) (1), 英語, 国際誌研究論文（学術雑誌）
- Springer Science and Business Media Deutschland GmbH, 2021年12月, Journal of Ophthalmic Inflammation and Infection, 11(1) (1), 英語研究論文（学術雑誌）
- PURPOSE: To determine the baseline characteristics of patients with central retinal vein occlusion (CRVO) that were significantly associated with the best-corrected visual acuity (BCVA) at the initial examination. METHODS: This was a retrospective multicenter study using the medical records registered in 17 ophthalmological institutions in Japan. Patients with untreated CRVO (≥20-years-of-age) who were initially examined between January 2013 and December 2017 were studied. The patients' baseline factors that were significantly associated with the BCVA at the initial examination were determined by univariate and multivariate linear regression analyses. RESULTS: Data from 517 eyes of 517 patients were analyzed. Univariate analyses showed that an older age (r = 0.194, p < 0.001) and the right eye (r = -0.103, p < 0.019) were significantly associated with poorer BCVA at the initial visit. Multivariate analyses also showed that an older age (β = 0.191, p < 0.001) and the right eye (β = -0.089, p = 0.041) were significantly associated with poorer BCVA at the initial visit. CONCLUSIONS: The results indicate that an older age, a known strong factor, and the right eye were significantly associated with poorer BCVA at the initial visit to the hospital. These results suggest that functional and/or anatomical differences between the right and left eyes may be involved in these results.2021年11月, Journal of clinical medicine, 10(23) (23), 英語, 国際誌研究論文（学術雑誌）
- Peripherin-2 (PRPH2) is one of the causative genes of inherited retinal dystrophy. While the gene is relatively common in Caucasians, reports from Asian ethnicities are limited. In the present study, we report 40 Japanese patients from 30 families with PRPH2-associated retinal dystrophy. We identified 17 distinct pathogenic or likely pathogenic variants using next-generation sequencing. Variants p.R142W and p.V200E were relatively common in the cohort. The age of onset was generally in the 40's; however, some patients had earlier onset (age: 5 years). Visual acuity of the patients ranged from hand motion to 1.5 (Snellen equivalent 20/13). The patients showed variable phenotypes such as retinitis pigmentosa, cone-rod dystrophy, and macular dystrophy. Additionally, intrafamilial phenotypic variability was observed. Choroidal neovascularization was observed in three eyes of two patients with retinitis pigmentosa. The results demonstrate the genotypic and phenotypic variations of the disease in the Asian cohort.2021年11月, Genes, 12(11) (11), 英語, 国際誌研究論文（学術雑誌）
- PURPOSE: Cytomegalovirus (CMV)-related keratouveitis elevates intraocular pressure (IOP). Antiviral therapy does not always control IOP and some patients do not tolerate systemic antiviral therapy because of the side effects. The purpose of this study is to evaluate the clinical characteristics of patients with CMV-related keratouveitis and determine the impact of glaucoma surgeries on the postoperative antiviral therapy regimen. METHODS: We enrolled twenty-two patients with CMV-DNA-positive keratouveitis between June 2012 and July 2019 in Kobe University Hospital. The following clinical parameters were collected: gender, age, history of previous intraocular surgery, antiviral medications, visual acuity, IOP, glaucoma drug score, corneal endothelial cells density, and the mean deviation of a Humphrey visual field test at the first visit and before and 1 year after glaucoma surgery. RESULTS: All twenty-two patients started on oral and/or topical antiviral therapy. Eighteen patients needed glaucoma surgery despite their antiviral medications. Nine patients underwent trabeculotomy (TLO) and nine underwent trabeculectomy (TLE) as the first surgical intervention. Six of patients who initially underwent TLO and two of the patients who initially underwent TLE required additional TLE within 1 year. Each of the 15 patients who underwent at least 1 TLE showed a reduction in the magnitude and variation of IOP and glaucoma drug scores and 13 patients were able to discontinue antiviral therapy. For the remaining 4 patients, IOP and inflammation were controlled but with antiviral medications. CONCLUSIONS: In patients with CMV-related keratouveitis, TLE decreases and stabilizes IOP and contributes to withdrawal from antiviral medications.2021年11月, BMC ophthalmology, 21(1) (1), 389 - 389, 英語, 国際誌研究論文（学術雑誌）
- 眼科臨床紀要会, 2021年11月, 眼科臨床紀要, 14(11) (11), 758 - 759, 日本語中心性漿液性脈絡網膜症患者における半量エネルギー光線力学的療法後低コントラスト視力
- Frontiers Media S.A., 2021年10月, Frontiers in Medicine, 8, 英語研究論文（学術雑誌）
- 眼科臨床紀要会, 2021年10月, 眼科臨床紀要, 14(10) (10), 690 - 691, 日本語標準治療からの逸脱が糖尿病黄斑浮腫の治療効果に及ぼす影響
- (一社)日本糖尿病合併症学会, 2021年09月, 糖尿病合併症, 35(Suppl.1) (Suppl.1), 252 - 252, 日本語糖尿病黄斑浮腫におけるen face slab OCT imagingと長期視力予後
- 眼科臨床紀要会, 2021年07月, 眼科臨床紀要, 14(7) (7), 452 - 452, 日本語視神経挫滅後のアクアポリン9ノックアウトマウスにおける網膜神経節細胞の機能低下と乳酸輸送障害の関係
- Elsevier Inc., 2021年06月, American Journal of Ophthalmology Case Reports, 22, 英語研究論文（学術雑誌）
- PURPOSE: To evaluate the short-term change in choroidal structure following adalimumab (ADA) treatment in refractory noninfectious uveitis. METHODS: This was a retrospective study of 33 eyes from 18 patients with refractory noninfectious uveitis. Subfoveal choroidal thickness (SFCT), the choroidal stromal index (CSI) defined as the proportion of stromal area to the total choroidal area were used as choroidal imaging parameters and were evaluated by enhanced depth imaging optical coherence tomography (EDI-OCT). The change in these parameters in the 2 months following initiation of ADA was analysed. A linear mixed-effect model was used to assess the effect of ADA treatment. RESULTS: The causes of uveitis were Vogt-Koyanagi-Harada disease (VKHD) (42.4%), presumed autoimmune retinopathy (15.2%), others (12.1%) and unclassified (30.3%). In the analysis of all eyes, the SFCT was 309.7 ± 113.1 μm at baseline, 295.7 ± 114.5 μm at 1 month and 275.2 ± 98.8 μm at 2 months after ADA initiation (P < 0.001). The CSI was 0.275 ± 0.050 at baseline, 0.273 ± 0.068 at 1 month and 0.273 ± 0.046 at 2 months (P = 0.785). In the subgroup analysis, the SFCT decreased significantly from baseline to 2 months in VKHD eyes (P = 0.007) and unclassified eyes (P = 0.034). There was no significant change in CSI in either subgroup. CONCLUSIONS: In the assessment of short-term response to ADA treatment in uveitic eyes, using EDI-OCT, the SFCT appears to be more effective as a choroidal imaging biomarker than the CSI, especially in VKHD eyes.2021年05月, Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 259(5) (5), 1273 - 1280, 英語, 国際誌研究論文（学術雑誌）
- To demonstrate the long-term effect of cystotomy with or without fibrinogen clot removal for treatment-resistant cystoid macular edema (CME) secondary to branch retinal vein occlusion (BRVO). Retrospective clinical study. We retrospectively analyzed medical records of 22 eyes of 22 patients with treatment-resistant CME secondary to BRVO with 12 months observation after cystotomy with or without fibrinogen clot removal. Patients included 11 women and 11 men. The mean ± SD age was 72.7 ± 10.2 years. LogMAR-converted best corrected visual acuity (BCVA) was statistically better at 12 months after surgery (0.30 ± 0.30) than preoperative BCVA (0.39 ± 0.27) (p = 0.01). The central sensitivity of microperimetry (dB) was maintained during follow-up (preoperative sensitivity: 25.4 ± 4.1, postoperative sensitivity at 12 months after the surgery: 25.9 ± 4.2, p = 0.69). Twelve months after surgery, there was a significant improvement in the central retinal thickness (CRT) on optical coherence tomography (OCT) (303.7 ± 80.1) (μm) compared with the preoperative CRT (524.2 ± 114.8) (p < 0.01). In 12 months, CME recurred in 3 of 22 eyes. The preoperative reflectivity in cystoid cavity on OCT was significantly higher in patients with fibrinogen clot removal (n = 5) than in patients without fibrinogen clot removal (n = 17) (p < 0.01). For treatment-resistant CME secondary to BRVO, Cystotomy with or without fibrinogen clot removal may be one of the treatment options.2021年04月, Scientific reports, 11(1) (1), 8460 - 8460, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Specific postoperative complications, such as tube exposure and conjunctival erosion, have occurred despite the favorable surgical outcomes of tube shunt surgeries for refractory glaucoma. The new autologous scleral pocket technique is performed by inserting the tube into the vitreous cavity without using a donor scleral patch. The purpose of this study was to evaluate the surgical results of Ahmed glaucoma valve (AGV) implantation using this technique for neovascular glaucoma (NVG), which is one of the representative refractory types of glaucoma. This observational retrospective case series included 15 consecutive eyes of 15 patients with NVG who had undergone AGV implantation at Kobe University between January 2018 and December 2019. The mean preoperative intraocular pressure (IOP) was 37.2 ± 13.8 mmHg and the glaucoma drug score was 4.2 ± 2.2. The mean IOP and glaucoma drug score at 1 year postoperatively decreased to 15.0 ± 4.6 mmHg and 1.3 ± 2.0, respectively (p < 0.001). No significant change in the corneal endothelial cell density following surgery was observed (p = 0.09); however, one patient required an additional trabeculectomy at 7 months postoperatively. No cases of tube exposure or conjunctival erosion were observed at 1 year postoperatively. These results indicated the effectiveness and safety of this technique in patients with NVG.2021年04月, Journal of clinical medicine, 10(8) (8), 英語, 国際誌[査読有り]研究論文（学術雑誌）
- A 71-year-old man was diagnosed with squamous cell lung carcinoma with high expression of programmed cell death ligand 1 (PDL1) (cT4N1M1b stage IVA). He was treated with pembrolizumab, but 14 days later, he suffered from pembrolizumab-related retinal vasculitis as an immune-related adverse event (irAE). The symptoms were ameliorated by oral corticosteroids. We succeeded in switching to topical treatment as early as possible with the help of an ophthalmologist. Six months after discontinuing treatment with oral prednisolone, hypophysitis and thyroiditis occurred in six cycles of pembrolizumab. Finally, he suffered from three irAEs, but the antitumour effect resulted in a remarkable response.2021年04月, Respirology case reports, 9(4) (4), e00730, 英語, 国際誌
- This retrospective study was conducted to investigate the clinical factors associated with low-contrast visual acuity after reduced-fluence photodynamic therapy (RFPDT) in patients with resolved central serous chorioretinopathy (CSC) and good baseline visual acuity. A total of 45 eyes of 45 patients with resolved CSC at post-RFPDT and best-corrected visual acuity of >1.0 (logarithm of the minimal angle of resolution [logMAR], 0) at baseline were examined. Visual acuities of both eyes were measured at four contrast levels (100%, 25%, 12%, and 6%) at post-RFPDT. The low-contrast visual acuity (6%, 12%, and 25%) was significantly lower than the 100% contrast visual acuity in the affected eyes. Visual acuities of affected eyes were significantly worse than those of fellow eyes at any contrast levels. The degree of changes in 6% and 100% contrast visual acuities was significantly greater in affected eyes than that in fellow eyes (p < 0.05). The 6% contrast visual acuities in affected eyes at post-RFPDT were significantly associated with the symptom duration (p < 0.05). Patients with a long duration of symptoms might have disturbed low-contrast visual acuities at post-RFPDT even if their baseline visual acuities were good.2021年03月, Pharmaceuticals (Basel, Switzerland), 14(4) (4), 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Bacterial endophthalmitis is an intraocular infection that causes rapid vison loss. Pathogens can infect the intraocular space directly (exogenous endophthalmitis (ExE)) or indirectly (endogenous endophthalmitis (EnE)). To identify predictive factors for the visual prognosis of Japanese patients with bacterial endophthalmitis, we retrospectively examined the bacterial endophthalmitis characteristics of 314 Japanese patients and performed statistics using these clinical data. Older patients, with significantly more severe clinical symptoms, were prevalent in the ExE group compared with the EnE group. However, the final best-corrected visual acuity (BCVA) was not significantly different between the ExE and EnE groups. Bacteria isolated from patients were not associated with age, sex, or presence of eye symptoms. Genus Streptococcus, Streptococcus pneumoniae, and Enterococcus were more prevalent in ExE patients than EnE patients and contributed to poor final BCVA. The presence of eye pain, bacterial identification, and poor BCVA at baseline were risk factors for final visual impairment.MDPI AG, 2021年03月, Pathogens, 10(4) (4), 390 - 390[査読有り]研究論文（学術雑誌）
- Multidrug resistance protein 4 (MRP4) is an energy-dependent membrane transporter responsible for cellular efflux of a broad range of xenobiotics and physiological substrates. In this trial, we aimed to investigate the coeffects of aging and MRP4 deficiency using gene expression microarray and morphological and electrophysiological analyses of mouse retinas. Mrp4-knockout (null) mice and wild-type (WT) mice were reared in the same conditions to 8-12 weeks (young) or 45-55 weeks (aged). Microarray analysis identified 186 differently expressed genes from the retinas of aged Mrp4-null mice as compared to aged WT mice, and subsequent gene ontology and KEGG pathway analyses showed that differently expressed genes were related to lens, eye development, vision and transcellular barrier functions that are involved in metabolic pathways or viral infection pathways. No significant change in thickness was observed for each retinal layer among young/aged WT mice and young/aged Mrp4-null mice. Moreover, immunohistochemical analyses of retinal cell type did not exhibit an overt change in the cellular morphology or distribution among the four age/genotype groups, and the electroretinogram responses showed no significant differences in the amplitude or the latency between aged WT mice and aged Mrp4-null mice. Aging would be an insufficient stress to cause some damage to the retina in the presence of MRP4 deficiency.2021年03月, Antioxidants (Basel, Switzerland), 10(3) (3), 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (公財)日本眼科学会, 2021年03月, 日本眼科学会雑誌, 125(臨増) (臨増), 212 - 212, 日本語VKH病及び眼サルコイドーシス再燃時における全身ステロイド薬の使用実態調査
- (公財)日本眼科学会, 2021年03月, 日本眼科学会雑誌, 125(臨増) (臨増), 212 - 212, 日本語VKH病及び眼サルコイドーシス再燃時における全身ステロイド薬の使用実態調査[査読有り]
- This multicenter retrospective study was conducted to evaluate the 1-year treatment outcome of photodynamic therapy (PDT) combined with anti-vascular endothelial growth factor (VEGF) therapy for pachychoroid neovasculopathy (PNV). A total of 42 eyes of 42 patients with treatment-naïve PNV who were treated with PDT combined with intravitreal injections of an anti-VEGF agent (ranibizumab or aflibercept) for 1 year. All eyes showed exudative and/or hemorrhagic changes that affected the fovea at baseline. After the initial combination therapy, subfoveal choroidal thickness (SCT) and central retinal thickness (CRT) were significantly reduced and were maintained as such for 12 months (P < 0.01 in SCT and CRT). The best-corrected visual acuity (BCVA) (0.19 ± 0.30 at baseline) significantly improved at 3 months (0.15 ± 0.29, P < 0.05) and further improved at 12 months (0.10 ± 0.30, P < 0.01) when compared to that at baseline. After the initial combination therapy, 32 eyes (76.2%) required no additional treatments for 12 months. The mean number of additional PDT and intravitreal injections of anti-VEGF agents was 0.1 ± 0.3 and 0.9 ± 1.9, respectively. Of the 42 eyes included in this study, 22 eyes (52.4%) had polypoidal lesions at baseline. No significant differences in SCT, CRT, or BCVA were observed at any time points between eyes with and without polypoidal lesions. Of 20 eyes without polypoidal lesions, only 1 eye (5.0%) needed additional treatments. PNV, especially without polypoidal lesions, can be treated effectively with PDT combined with anti-VEGF therapy with few sessions.2021年, PloS one, 16(3) (3), e0248760, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) is the standard treatment modality in various types of retinal diseases. However, endophthalmitis remains the most serious complication. Despite the lack of evidence that antibiotics prevent endophthalmitis, topical antibiotics are still used routinely in Japan. We conducted a retrospective multicenter study by analyzing records from patients who underwent IVI of anti-VEGF agents with or without antibiotic treatment. In the analysis of a total of 147,440 eyes, the incidence of endophthalmitis was 0.007%: 0.005% with no use of antibiotics, 0.009% with antibiotic pretreatment, 0.012% with posttreatment, and 0.005% with pre- and posttreatment. There was no statistically significant difference among the four groups (chi-square test, p = 0.57). Most facilities used masks, sterilized gloves, and drapes. Nine of the 10 eyes that developed endophthalmitis received topical antibiotics, and all infected eyes underwent IVI with aflibercept, not the prefilled syringe delivery system. In four patients who received multiple IVI, the detection of causative bacteria revealed resistance to used antibiotics. Data from this large population, treated with or without antibiotics, suggests that antibiotic prophylaxis does not reduce the rate of endophthalmitis after IVI.2020年12月, Scientific reports, 10(1) (1), 22122 - 22122, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (公社)日本視能訓練士協会, 2020年12月, 日本視能訓練士協会誌, 49, 246 - 246, 日本語
- 眼科臨床紀要会, 2020年11月, 眼科臨床紀要, 13(11) (11), 756 - 756, 日本語視力良好な中心性漿液性脈絡網膜症における治療後不等像視の関連因子についての検討
- Aquaporin 9 (AQP9) is an aquaglyceroporin that can transport lactate. Accumulating evidence suggests that astrocyte-to-neuron lactate shuttle (ANLS) plays a critical role in energy metabolism in neurons, including retinal ganglion cells (RGCs). To test the hypothesis that AQP9, in concert with monocarboxylate transporters (MCTs), participates in ANLS to maintain function and survival of RGCs, Aqp9-null mice and wild-type (WT) littermates were subjected to optic nerve crush (ONC) with or without intravitreal injection of an MCT2 inhibitor. RGC density was similar between the Aqp9-null mice and WT mice without ONC, while ONC resulted in significantly more RGC density reduction in the Aqp9-null mice than in the WT mice at day 7. Positive scotopic threshold response (pSTR) amplitude values were similar between the two groups without ONC, but were significantly more reduced in the Aqp9-null mice than in the WT mice 7days after ONC. MCT2 inhibitor injection accelerated RGC death and pSTR amplitude reduction only in the WT mice with ONC. Immunolabeling revealed that both RGCs and astrocytes expressed AQP9, that ONC predominantly reduced astrocytic AQP9 expression, and that MCTs 1, 2, and 4 were co-localized with AQP9 at the ganglion cell layer. These retinal MCTs were also co-immunoprecipitated with AQP9 in the WT mice. ONC decreased the co-immunoprecipitation of MCTs 1 and 4, but did not impact co-immunoprecipitation of MCT2. Retinal glucose transporter 1 expression was increased in Aqp9-null mice. Aqp9 gene deletion reduced and increased the intraretinal L-lactate and D-glucose concentrations, respectively. Results suggest that AQP9 acts as the ANLS to maintain function and survival of RGCs.2020年08月, Molecular neurobiology, 57(11) (11), 4530 - 4548, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- PURPOSE: To show the long-term effect of the cystotomy with or without fibrinogen clot removal for the refractory cystoid macular edema (CME) secondary to diabetic retinopathy (DR). METHODS: Retrospective analyses of the medical records of 30 eyes of 30 patients with refractory CME secondary to DR who had followed-up for 12 months after the surgery were performed. RESULTS: There were 15 men and 15 women. The mean±SD age was 68.4±7.9 years. The best corrected visual acuity (BCVA) (logMAR) at 12 months after the surgery (0.33±0.25, Snellen equivalent (SE), 20/42) was statistically better than the preoperative BCVA (0.45±0.33, SE, 20/56) (p<0.01). The central sensitivity on microperimetry (dB) was not statistically changed between preoperatively (24.0±4.9) and 12 months after the surgery (24.1±4.0) (p=0.75). The central retinal thickness (CRT) on optical coherence tomography (OCT) (μm) at 12 months after the surgery (300.3±99.0) was statistically improved compared with the preoperative CRT (565.6±198.7) (p<0.01). During the follow-up period, CME relapsed in 7 of 30 eyes. The preoperative cystoid cavity reflectivity on OCT in patients with fibrinogen clot removal (n=16) was significantly higher compared with that in patients without fibrinogen clot removal (n=14) (p<0.04). CONCLUSION: The cystotomy with or without fibrinogen clot removal may be a promising treatment option for refractory CME secondary to DR.2020年07月, Retina (Philadelphia, Pa.), 41(4) (4), 844 - 851, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Elsevier Inc, 2020年06月, American Journal of Ophthalmology Case Reports, 18, 英語研究論文（学術雑誌）
- (公財)日本眼科学会, 2020年06月, 日本眼科学会雑誌, 124(6) (6), 465 - 471, 日本語
- (公財)日本眼科学会, 2020年06月, 日本眼科学会雑誌, 124(6) (6), 465 - 471, 日本語治療維持期の視力不良な滲出型加齢黄斑変性患者の固視[査読有り]
- PURPOSE: To show the usefulness of the intraoperative three-dimensional fluorescein angiography (3D-FA)-guided pars plana vitrectomy. METHODS: The NGENUITY 3D visualization system was used for the digital assisted vitrectomy. Three-dimensional fluorescein angiography-guided pars plana vitrectomy was performed in three patients with vitreous hemorrhage secondary to proliferative diabetic retinopathy. We investigated both whether several angiographic findings can be successfully displayed on the screen during 3D-FA and whether pars plana vitrectomy can be performed simultaneously on the same screen while implementing 3D-FA. RESULTS: In all cases, the abnormal FA findings including hypofluorescence due to non-perfusion areas, and the hyperfluorescence due to macular edema and fibrovascular proliferative membrane were successfully displayed on the screen. The segmentation and delamination of fibrovascular proliferative membrane and panretinal photocoagulation for detected non-perfusion areas were able to be performed on the same screen while implementing 3D-FA. CONCLUSION: Three-dimensional fluorescein angiography-guided pars plana vitrectomy is a novel approach that fully utilizes the advantages of digital assisted vitrectomy and a promising option for the treatment of proliferative diabetic retinopathy.2020年04月, Retina (Philadelphia, Pa.), 英語, 国際誌[査読有り]研究論文（学術雑誌）
- BACKGROUND/AIMS: To investigate the yearly change of real-world outcomes for best corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve diabetic macular oedema (DMO). METHODS: Retrospective analysis of aggregated, longitudinal medical records obtained from 27 retina specialised institutions in Japan from Survey of Treatment for DMO database. A total of 2049 treatment-naïve centre involving DMO eyes of which the initial intervention started between 2010 and 2015, and had been followed for 2 years, were eligible. As interventions, antivascular endothelial growth factor (VEGF) agents, local corticosteroids, macular photocoagulation and vitrectomy were defined. In each eye, baseline and final BCVA, the number of each intervention for 2 years was extracted. Each eye was classified by starting year of interventional treatment. RESULTS: Although baseline BCVA did not change by year, 2-year improvement of BCVA had been increased, and reached to +6.5 letters in the latest term. There is little difference among starting year about proportions of eyes which BCVA gained >15 letters, in contrast to those which lost >15 letters were decreased by year. The proportion of eyes receiving anti-VEGF therapy was dramatically increased, while those receiving the other therapies were gradually decreased. The proportion of eyes which maintained socially good vision of BCVA>20/40 has been increased and reached to 59.0% in the latest term. CONCLUSION: For recent years, treatment patterns for DMO have been gradually but certainly changed; as a result, better visual gain, suppression of worsened eyes and better final BCVA have been obtained. Anti-VEGF therapy has become the first-line therapy and its injection frequency has been increasing.2020年03月, The British journal of ophthalmology, 104(12) (12), 1755 - 1761, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- OBJECTIVE: To evaluate the usefulness of en face slab optical coherence tomography (OCT) imaging for monitoring diabetic retinal neurodegeneration with supporting animal experimental data. RESEARCH DESIGN AND METHODS: We retrospectively examined 72 diabetic eyes over 3 years using Cirrus-HD OCT. Two-dimensional en face slab OCT images of the innermost retina were reconstructed and graded according to the ratio of dark area to total area, and relative red, green, and blue color area ratios were calculated and used as indexes for each en face slab OCT image. Values from en face OCT images were used for statistical analyses. To obtain insight into the pathogenesis of diabetic retinal neurodegeneration, we used the InsPr-Cre;Pdk1flox/flox diabetic mouse model. RESULTS: Both OCT grade and relative red color area ratio significantly increased with the advancing stage of diabetic retinopathy (p=0.018 and 0.006, respectively). After a mean follow-up period of 4.6 years, the trend was unchanged in the analyses of 42 untreated eyes (p<0.001 and 0.001, respectively). Visual acuity showed a weak but significant negative correlation with the red color ratio on en face slab OCT images, but central retinal thickness did not exhibit a clinically meaningful correlation with values obtained from en face slab OCT images. Immunohistochemical analyses of InsPr-Cre;Pdk1flox/flox diabetic mice demonstrated the loss of ganglion axon bundles and thinning of laminin without apparent retinal vascular change at the age of 20 weeks. CONCLUSIONS: En face slab OCT imaging would be a novel useful modality for the assessment of diabetic retinal neurodegeneration as it could detect subtle optical changes occurring in the innermost retina in diabetic eyes. Our animal experimental data suggest that dark areas observed on en face slab OCT images might be the impairment of the extracellular matrix as well as neurons.2020年03月, BMJ open diabetes research & care, 8(1) (1), 英語, 国際誌[査読有り]研究論文（学術雑誌）
- This retrospective study was conducted to investigate the predictive factors associated with metamorphopsia after reduced-fluence photodynamic therapy (RFPDT) in patients with central serous chorioretinopathy (CSC) with good baseline visual acuity. A total of 36 eyes of 36 consecutive patients with resolved CSC after RFPDT and best-corrected visual acuity (BCVA) better than 1.0 (logarithm of the minimal angle of resolution (logMAR) 0) at baseline were examined. Metamorphopsia was measured using M-CHARTS at 12 months after RFPDT. An average of the horizontal and vertical M-CHARTS scores was applied for defining the extent of metamorphopsia. The association between M-CHARTS score at 12 months after RFPDT and clinical parameters (age, sex, duration of symptoms, BCVA, and findings of optical coherence tomography (OCT)) was investigated at baseline or 12 months after RFPDT. The M-CHARTS score at 12 months correlated significantly with duration of symptoms (P = 0.005), baseline outer nuclear layer (ONL) thickness (P = 0.009), central foveal thickness (CFT) (P = 0.001) at 12 months, and ONL thickness (P = 0.001) at 12 months after RFPDT. In the multivariate analysis of baseline-related factors, thinner ONL thickness before RFPDT (P = 0.010) was significantly associated with large metamorphopsia at 12 months after RFPDT in CSC patients with good baseline BCVA. Baseline ONL thickness may be a useful predictive factor of metamorphopsia after RFPDT in CSC patients with good baseline BCVA.2020年, PloS one, 15(10) (10), e0240557, 英語, 国際誌研究論文（学術雑誌）
- Genetic factors associated with treatment response to reduced-fluence photodynamic therapy for chronic central serous chorioretinopathy.Purpose: Reduced-fluence photodynamic therapy (RFPDT) has proven effective for some patients with chronic central serous chorioretinopathy (cCSC). Several clinicodemographic factors influencing treatment response have been identified, but associations with genetic factors have not been examined. Therefore, we investigated the associations of single nucleotide polymorphisms (SNPs) implicated in cCSC pathogenesis with clinical outcome following RFPDT. Methods: This was a retrospective study of 87 eyes from 87 patients with cCSC who underwent RFPDT and were followed up for more than 12 months. Patients were divided into a good response group (53 patients) and a poor response group (34 patients) based on either persistence or recurrence of subretinal fluid detected with spectral domain optical coherence tomography after the first application of RFPDT. SNPs in the genes encoding age-related maculopathy susceptibility protein 2 (ARMS2, SNP rs10490924) and complement factor H (CFH, SNP rs800292) were genotyped using TaqMan technology. Results: There were no statistically significant differences in the baseline characteristics between the response groups except the degree of hyperfluorescence on indocyanine green angiography (ICGA; p = 0.011). The minor (T) allele frequency of ARMS2 (rs10490924) were statistically significantly lower in the good response group than in the poor response group (24.0% versus 41.0%, p = 0.021). Further, the good response frequency was statistically significantly lower in patients with at least one minor allele (GT or TT) compared to the homozygous major allele group (GG; p<0.05). The baseline best-corrected visual acuity (BCVA) at 12 months after RFPDT was statistically significantly better in the GG carriers than in the GT or TT carriers (p<0.01). Logistic regression analysis showed less intense hyperfluorescence on ICGA, and the T allele of ARMS2 (rs10490924) was statistically significantly associated with poor response to PDT treatment (p = 0.012, p = 0.039, respectively). Conclusions: Carriers of the ARMS2 rs10490924 minor allele (GT or TT) demonstrated a higher subretinal fluid persistence or recurrence rate and poorer visual outcome following RFPDT. In addition to the ICGA findings, genotyping of ARMS2 (rs10490924) may assist in the selection of patients with cCSC most likely to benefit from RFPDT.2020年, Molecular vision, 26, 505 - 509, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- BACKGROUND/AIMS: To investigate real-world outcomes for best-corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve, centr-involving diabetic macular oedema (DME). METHODS: Retrospective analysis of longitudinal medical records obtained from 27 institutions specialising in retinal diseases in Japan. A total of 2049 eyes with treatment-naïve DME commencing intervention between 2010 and 2015 who were followed for 2 years were eligible. Interventions for DME included anti-vascular endothelial growth factor (VEGF) therapy, local corticosteroid therapy, macular photocoagulation and vitrectomy. Baseline and final BCVA (logMAR) were assessed. Eyes were classified by the treatment pattern, depending on whether anti-VEGF therapy was used, into an anti-VEGF monotherapy group (group A), a combination therapy group (group B) and a group without anti-VEGF therapy (group C). RESULTS: The mean 2-year improvement of BCVA was -0.04±0.40 and final BCVA of >20/40 was obtained in 46.3% of eyes. Based on the treatment pattern, there were 427 eyes (20.9%) in group A, 807 eyes (39.4%) in group B and 815 eyes (39.8%) in group C. Mean improvement of BCVA was -0.09±0.39, -0.02±0.40 and -0.05±0.39, and the percentage of eyes with final BCVA of >20/40 was 49.4%, 38.9%, and 52.0%, respectively. CONCLUSION: Following 2-year real-world management of treatment-naïve DME in Japan, BCVA improved by 2 letters. Eyes treated by anti-VEGF monotherapy showed a better visual prognosis than eyes receiving combination therapy. Despite treatment for DME being selected by specialists in consideration of medical and social factors, a satisfactory visual prognosis was not obtained, but final BCVA remained >20/40 in half of all eyes.2019年11月, The British journal of ophthalmology, 104(9) (9), 1209 - 1215, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- 日本視能矯正学会, 2019年11月, 日本視能矯正学会プログラム抄録集, 60回, 89 - 89, 日本語視力良好な中心性漿液性脈絡網膜症における治療後不等像視の関連因子についての検討[査読有り]
- 眼科臨床紀要会, 2019年11月, 眼科臨床紀要, 12(11) (11), 834 - 834, 日本語滲出型加齢黄斑変性の固視に関する検討[査読有り]
- BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease is a T-cell-mediated autoimmune disorder characterized by bilateral granulomatous panuveitis with various systemic manifestations. Although VKH disease rarely occurs in the pediatric population, the clinical course tends to be aggressive, and the visual prognosis is worse than that in adult patients due to severe ocular complications secondary to recurrent inflammation. CASE PRESENTATION: A 3-year-old girl with probable VKH was referred to Kobe University Hospital. She had severe bilateral panuveitis with posterior synechiae of the iris, marked optic disk swelling, and serous retinal detachment in both eyes, and her best corrected visual acuities (BCVAs) were 20/200 OD and 20/125 OS. A third course of therapy was administered because serous retinal detachment remained after two courses of therapy. She was treated with three courses of high-dose intravenous corticosteroid therapy, followed by slow tapering of oral corticosteroids. Her BCVAs recovered to 20/16 OU, and relapse of ocular inflammation and side effect of treatment were not observed during the 1.5-year follow-up period. CONCLUSIONS: We experienced a pediatric patient with probable VKH disease who was treated with three courses of high-dose intravenous corticosteroid therapy. With the favorable clinical course in our patient, initial treatment with repeated high-dose intravenous corticosteroid therapy might be beneficial in pediatric VKH disease.2019年08月, BMC ophthalmology, 19(1) (1), 179 - 179, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- 日本糖尿病眼学会, 2019年07月, 日本糖尿病眼学会誌, 23, 138 - 138, 日本語糖尿病性黄斑浮腫に対するアフリベルセプト治療に影響する因子についての検討
- Purpose: The present study aimed to assess the ability of en face slab images of maculae to detect residual nerve fiber bundles in eyes with advanced glaucoma. Methods: This study included 36 eyes with diffuse thinning of the ganglion cell and inner plexiform layers (GCL+IPL). Inclusion criterion was GCL+IPL thickness of <1% of the normative database level as detected using optical coherence tomography (OCT). En face slab images (50-μm thickness) were reconstructed from the macular cube scan data using advanced visualization settings. Thereafter, we assessed the agreement of the locations between hyperreflective nerve fiber bundles and normal points in the Humphrey visual field test 10-2 pattern deviation (PD) plots. Additionally, total deviation (TD) corresponding to hyperreflective and hyporeflective areas was compared. Results: Hyperreflective areas were detected in 31 out of 36 eyes; all 31 eyes exhibited at least one normal PD point despite the substantial GCL+IPL thinning in the macular region. Two eyes with abnormalities in all PD points showed no hyperreflective area. The remaining three eyes had normal PD points despite the lack of high reflectivity areas in the slab images. Therefore, 91.7% of eyes showed agreement between en face slab images and PD plots. Moreover, hyperreflective areas demonstrated significantly better TD than hyporeflective areas. Conclusions: En face slab images of maculae were able to reveal the residual nerve fiber bundles in the eyes with advanced glaucoma despite the GCL+IPL thickness in the maculae being diffusely and substantially reduced.2019年07月, Investigative ophthalmology & visual science, 60(8) (8), 2811 - 2821, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (公財)日本眼科学会, 2019年02月, 日本眼科学会雑誌, 123(2) (2), 121 - 127, 日本語続発緑内障に対するテノン開創器を用いた線維柱帯切除術の短期成績
- Transforming growth factor beta-induced (TGFBI)-associated corneal dystrophies are a group of inherited progressive corneal diseases. One of these TGFBI-associated corneal dystrophies is Avellino corneal dystrophy, an autosomal dominant corneal dystrophy characterized by multiple asymmetric stromal opacities that potentially impair vision. Recently, a case with corneal dystrophy complicated by nephropathy possessing a pathogenic variant of the TGFBI gene was reported for the first time. Here, we report the second case with the same condition and the same mutation in the TGFBI gene. The patient was an 18-year-old male. He and his father had already been diagnosed with corneal dystrophy. Proteinuria was revealed in the patient during urine screening at school. Since his serum creatinine level was raised, a percutaneous renal biopsy was performed. Light microscopy demonstrated oligomeganephronia. Electron microscopy demonstrated an irregular basement membrane. TGFBI was analyzed by direct sequencing. A heterozygous mutation c.371G > A in exon 4, which caused an amino acid substitution from arginine to histidine at codon 124, was identified in the patient and his father. Although only one case of TGFBI-associated corneal dystrophy and nephropathy has been reported, our case's clinical and pathological findings were almost identical to those in that reported case. Further investigations of this new disease entity should be reported to all nephrologists and ophthalmologists.2019年02月, CEN case reports, 8(1) (1), 14 - 17, 英語, 国内誌[査読有り]研究論文（学術雑誌）
- 2019年01月, Case Reports in Ophthalmology, 10(1) (1), 5 - 10[査読有り]研究論文（学術雑誌）
- Purpose: This study aimed to evaluate the long-term efficacy and safety of infliximab (IFX) and cyclosporine (CsA) combination therapy for refractory uveoretinitis in Behçet's disease (BD). Patients and methods: The study involved a retrospective review of the medical records of 11 patients with Behçet's uveoretinitis refractory to conventional treatment who had been treated with IFX+CsA combination therapy. The frequency of ocular inflammatory attacks and a Behçet's disease ocular attack score 24 (BOS24) were used as indices for the evaluation of efficacy during each 6-month period prior to and following initiation of therapy. For the assessment of safety, adverse events (AEs) were recorded throughout the treatment period. Results: The patients had received IFX+CsA combination therapy for 5.6±2.3 years. The frequency of ocular attacks per 6-month period decreased markedly from 2.9±1.6 during the baseline period to 0.6±0.9 during months 1-6, 0.5±0.9 during months 7-12, 0.3±0.5 during months 13-18, 0.3±0.7 during months 19-24, and 0.0±0.0 thereafter (P=0.003). The BOS24 score per ocular attack significantly decreased from 5.2±2.4 during the baseline period to 1.5±2.1 during months 1-6, 1.7±3.1 during months 7-12, 1.6±2.9 during months 13-18, and 0.4±1.0 during months 19-24 (P=0.002). No serious AEs were observed, with the exception of urinary tract infection and cataract progression. Two patients exhibited transient elevation of the serum creatinine level, which was normalized following a reduction in the dose of CsA. Conclusion: For refractory Behçet's uveoretinitis, IFX+CsA combination therapy offers a promising treatment option as it appears to have an acceptable safety profile and can reduce the frequency and severity of ocular inflammatory attacks over a long period of time.2019年, Clinical ophthalmology (Auckland, N.Z.), 13, 521 - 527, 英語, 国際誌[査読有り]
- 眼科臨床紀要会, 2018年11月, 眼科臨床紀要, 11(11) (11), 838 - 839, 日本語抗血管内皮増殖因子薬硝子体内注射で治療開始した網膜静脈分枝閉塞症の治療休止割合
- 日本臨床免疫学会, 2018年11月, 日本臨床免疫学会総会プログラム・抄録集, 46回, 81 - 81, 日本語眼免疫の特殊性と非感染性ぶどう膜炎
- (一社)日本糖尿病合併症学会, 2018年10月, 糖尿病合併症, 32(Suppl.1) (Suppl.1), 298 - 298, 日本語糖尿病黄斑浮腫治療成績とOCT en face slab像の関係
- (一社)日本糖尿病合併症学会, 2018年10月, 糖尿病合併症, 32(Suppl.1) (Suppl.1), 125 - 125, 日本語全身加療と局所変化 全身加療と糖尿病網膜神経変性
- 眼科臨床紀要会, 2018年10月, 眼科臨床紀要, 11(10) (10), 763 - 763, 日本語視力良好なポリープ状脈絡膜血管症への光線力学的療法単独とアフリベルセプト併用療法
- 日本糖尿病眼学会, 2018年09月, 日本糖尿病眼学会誌, 22, 134 - 134, 日本語実臨床における糖尿病黄斑浮腫に対するラニビズマブ硝子体注射の12ヵ月治療成績[査読有り]
- 2018年07月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 59(9) (9)Structural changes in the inner retina assessed by slab en face optical coherence tomography in diabetic eyes[査読有り]研究論文（学術雑誌）
- PURPOSE: The purpose of this study was to describe the initial experience, efficacy, and safety of ripasudil hydrochloride hydrate (ripasudil), a Rho-associated kinase inhibitor eye drop, for uveitic glaucoma. METHODS: In this retrospective case series, we retrieved the clinical data of 21 eyes from 19 patients with open-angle uveitic glaucoma who were treated with ripasudil at Kobe University Hospital. We analyzed the median intraocular pressure (IOP) reductions after ripasudil treatment and collected the information on the adverse events that were encountered during the course of this treatment period. RESULTS: The causes of uveitis were sarcoidosis (29%), Behçet's disease (14%), Vogt-Koyanagi-Harada disease (10%), others (15%), and unclassified (33%). Of total, 19 (90%) eyes were treated with topical, periocular, and/or systemic steroid therapies. The median number of glaucoma medications used before ripasudil treatment was 2, and the median follow-up time was 13 months. The median IOPs were 23 mmHg at baseline, 16 mmHg at 1 month, and 18 mmHg at 12 months with significant IOP reductions of - 3 mmHg at 1 month and - 2 mmHg at 12 months (P = 0.0050). Of total, 11 (52%) eyes with an IOP reduction ≥ 3 mmHg at 1 month (responders) showed a significant median IOP decrease at 12 months compared with non-responders (- 5 versus 0 mmHg, P = 0.0242). Two adverse events were observed: rashes on the back and transient conjunctival hyperemia. CONCLUSIONS: Ripasudil appears to be safe and substantially reduce IOP in eyes with uveitic glaucoma if the eye is a responder. Ripasudil could be an option for the treatment of uveitic glaucoma.2018年04月, Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 256(4) (4), 809 - 814, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (公財)日本眼科学会, 2018年03月, 日本眼科学会雑誌, 122(臨増) (臨増), 246 - 246, 日本語続発緑内障に対するテノン開創器を用いた線維柱帯切除術の短期成績
- (公財)日本眼科学会, 2018年03月, 日本眼科学会雑誌, 122(臨増) (臨増), 176 - 176, 日本語光干渉断層計slab en face像を用いた糖尿病網膜内層構造変化の評価
- (公財)日本眼科学会, 2018年03月, 日本眼科学会雑誌, 122(臨増) (臨増), 203 - 203, 日本語ポリープ状脈絡膜血管症へのアフリベルセプト併用光線力学療法後の網膜色素上皮萎縮
- (公財)日本眼科学会, 2018年03月, 日本眼科学会雑誌, 122(臨増) (臨増), 116 - 116, 日本語ベーチェット病の治療
- (公財)日本眼科学会, 2018年03月, 日本眼科学会雑誌, 122(臨増) (臨増), 166 - 166, 日本語アクアポリン9遺伝子欠損マウスにおける視神経挫滅後の網膜神経節細胞死
- (一社)日本神経学会, 2018年02月, 臨床神経学, 58(2) (2), 111 - 117, 日本語, 国内誌
- 2018年, 臨床神経学, 58(2) (2), 111 - 117, 日本語大脳石灰化病変を契機に診断に至ったTREX1 遺伝子変異に伴うretinal vasculopathy with cerebral leukoencephalopathy の1 例[査読有り]
- 眼科臨床紀要会, 2017年11月, 眼科臨床紀要, 10(11) (11), 932 - 932, 日本語網膜前膜術後の最高矯正視力予測因子の検討
- 眼科臨床紀要会, 2017年11月, 眼科臨床紀要, 10(11) (11), 941 - 941, 日本語ポリープ状脈絡膜血管症に対する光線力学療法3年予後に関連する遺伝子多型の検討
- 眼科臨床紀要会, 2017年11月, 眼科臨床紀要, 10(11) (11), 950 - 950, 日本語アキシチニブ内服中に著しい網膜循環障害をきたした1例
- Igaku-Shoin Ltd, 2017年10月, Japanese Journal of Clinical Ophthalmology, 71(10) (10), 1505 - 1511, 日本語Photodynamic therapy and intravitreal bevacizumab resulted in prolonged improvement of visual acuity in a case of choroidal osteoma with choroidal neovascularization研究論文（学術雑誌）
- (株)医学書院, 2017年10月, 臨床眼科, 71(10) (10), 1505 - 1511, 日本語臨床報告 光線力学療法とベバシズマブ硝子体注射により長期間視力が改善した脈絡膜骨腫に続発した脈絡膜血管新生の1例
- 眼科臨床紀要会, 2017年10月, 眼科臨床紀要, 10(10) (10), 856 - 857, 日本語網膜静脈分枝閉塞症に対するラニビズマブ硝子体注射12ヵ月後視力予後因子の検討
- (一社)日本糖尿病合併症学会, 2017年10月, 糖尿病合併症, 31(Suppl.1) (Suppl.1), 350 - 350, 日本語実臨床における糖尿病黄斑浮腫に対する抗VEGF薬硝子体注射の12ヵ月治療成績
- PURPOSE: Central serous chorioretinopathy (CSC) is a common choroidal disorder which often affects the vision of young adults. Although the molecular mechanisms associated with CSC remain unknown, correlations between steroid hormone use and CSC have been suspected. We investigated the choroidal status of CSC secondary to corticosteroid use. METHODS: The records of 25 eyes of 25 consecutive acute CSC cases secondary to corticosteroid use were reviewed retrospectively. Central choroidal thickness was measured by optical coherent tomography. Choroidal vessel dilation and choroidal vascular hyperpermeability were evaluated based on indocyanine green angiography findings. The parameters related to secondary CSC were compared with those of 25 eyes of 25 cases with acute idiopathic CSC. RESULTS: The mean central choroidal thickness of secondary CSC was 294.8 ± 95.0 μm, which was significantly thinner than that of idiopathic CSC (409.4 ± 124.7 μm, P = 0.00064). The proportion of the cases exhibiting choroidal vessel dilation was not significantly different between secondary CSC (52%) and idiopathic CSC (64%). The proportion of cases showing choroidal vascular hyperpermeability was significantly smaller in secondary CSC (62%) than idiopathic CSC (92%) (P = 0.028). CONCLUSION: The choroidal status in the acute phase of secondary CSC after corticosteroid use might be different from that of idiopathic CSC, which suggests a complex mechanism for CSC.2017年08月, Retina (Philadelphia, Pa.), 37(8) (8), 1562 - 1567, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (公財)日本眼科学会, 2017年03月, 日本眼科学会雑誌, 121(臨増) (臨増), 320 - 320, 日本語Vogt-小柳-原田病の12ヵ月治療成績と再発に関わるリスク因子の検討
- 2017年03月, Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 255(3) (3), 541 - 548, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- In the central nervous system, endothelial cells (ECs) and pericytes (PCs) of blood vessel walls cooperatively form a physical and chemical barrier to maintain neural homeostasis. However, in diabetic retinopathy (DR), the loss of PCs from vessel walls is assumed to cause breakdown of the blood-retina barrier (BRB) and subsequent vision-threatening vascular dysfunctions. Nonetheless, the lack of adequate DR animal models has precluded disease understanding and drug discovery. Here, by using an anti-PDGFRβ antibody, we show that transient inhibition of the PC recruitment to developing retinal vessels sustained EC-PC dissociations and BRB breakdown in adult mouse retinas, reproducing characteristic features of DR such as hyperpermeability, hypoperfusion, and neoangiogenesis. Notably, PC depletion directly induced inflammatory responses in ECs and perivascular infiltration of macrophages, whereby macrophage-derived VEGF and placental growth factor (PlGF) activated VEGFR1 in macrophages and VEGFR2 in ECs. Moreover, angiopoietin-2 (Angpt2) upregulation and Tie1 downregulation activated FOXO1 in PC-free ECs locally at the leaky aneurysms. This cycle of vessel damage was shut down by simultaneously blocking VEGF, PlGF, and Angpt2, thus restoring the BRB integrity. Together, our model provides new opportunities for identifying the sequential events triggered by PC deficiency, not only in DR, but also in various neurological disorders.2017年02月, JCI insight, 2(3) (3), e90905, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (株)メディカル葵出版, 2017年02月, あたらしい眼科, 34(2) (2), 280 - 282, 日本語
- 2016年09月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 57(12) (12), 英語Ability of OCT angiography to detect choroidal neovascularization in retinal pigment epithelial detachment associated with chronic central serous chorioretinopathy.[査読有り]研究論文（学術雑誌）
- (公財)日本眼科学会, 2016年03月, 日本眼科学会雑誌, 120(臨増) (臨増), 152 - 152, 日本語眼科基礎研究スキルトランスファー 基本戦術とスキルを身につけよう 遺伝子発現解析を用いた眼疾患・基礎研究
- (公財)日本眼科学会, 2016年03月, 日本眼科学会雑誌, 120(臨増) (臨増), 308 - 308, 日本語加齢性網膜変化におけるmultidrug resistance protein 4(Mrp4)の役割
- (一社)日本糖尿病合併症学会, 2015年11月, 糖尿病合併症, 29(Suppl.1) (Suppl.1), 221 - 221, 日本語糖尿病黄斑浮腫に対するRanibizumab 1回投与後の経過に関する検討
- Myopia can cause severe visual impairment. Here, we report a two-stage genome-wide association study for three myopia-related traits in 9,804 Japanese individuals, which was extended with trans-ethnic replication in 2,674 Chinese and 2,690 Caucasian individuals. We identify WNT7B as a novel susceptibility gene for axial length (rs10453441, Pmeta=3.9 × 10(-13)) and corneal curvature (Pmeta=2.9 × 10(-40)) and confirm the previously reported association between GJD2 and myopia. WNT7B significantly associates with extreme myopia in a case-control study with 1,478 Asian patients and 4,689 controls (odds ratio (OR)meta=1.13, Pmeta=0.011). We also find in a mouse model of myopia downregulation of WNT7B expression in the cornea and upregulation in the retina, suggesting its possible role in the development of myopia.2015年03月, Nature communications, 6, 6689 - 6689, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- PURPOSE: To compare the response to ranibizumab between patients with typical neovascular age-related macular degeneration (tAMD) and those with polypoidal choroidal vasculopathy (PCV), and to determine the predictors for the outcomes. METHODS: Fifty-nine eyes from 59 consecutive patients (tAMD: 27 eyes, PCV: 32 eyes) were treated with three monthly ranibizumab injections followed by as-needed retreatment. Best-corrected visual acuity (BCVA) and morphological parameters were evaluated over 24 months of follow-up. RESULTS: The mean BCVA in tAMD and PCV patients was significantly improved at 3 months (-0.22 and -0.09 logMAR units, respectively). The improvement in BCVA was sustained up to 24 months in tAMD (p = 0.01) but not in PCV patients. The significant predictor for good response to ranibizumab in tAMD patients was the improvement of BCVA at 3 months, whereas that in PCV patients was the anatomical resolution at 3 months. CONCLUSIONS: Ranibizumab is an effective therapy for tAMD and PCV over 24 months. The predictors for good outcome might be different between tAMD and PCV.2015年, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde, 234(1) (1), 33 - 9, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- PURPOSE: Our aim was to use molecular biological methods to study evidence of autoimmune disease in five patients with acute zonal occult outer retinopathy (AZOOR). METHODS: Ophthalmologic data and sera were collected from all patients, who underwent visual field (VF) examination, optical coherence tomography (OCT), and multifocal electroretinogram (mfERG) recording. Serum was prepared from each patient's blood and analyzed for antiretinal antibody activity using immunohistochemistry and Western blot analysis on mouse and human retinas. We also searched for antigen proteins using mass spectrometry. RESULTS: Symptoms were blurred vision in three patients and VF defects in two; all had enlargement of the Mariotte blind spot by VF testing. OCT findings in areas corresponding to the scotoma revealed disruptions of junction borders between inner and outer segment lines. mfERGs amplitudes were reduced in each corresponding scotoma area. Immunohistochemical serum staining revealed the target antigen was present in all photoreceptors of the mouse sensory retina. Western blot analysis using patient serum samples revealed some possible candidate antigens. Mass spectrometry could not determine the causative antigen; however, a list of candidates was discovered. CONCLUSION: We determined that AZOOR could be an autoimmune disease. All AZOOR patients tested using molecular biological methods had antiretinal antigens.2014年11月, Japanese journal of ophthalmology, 58(6) (6), 462 - 72, 英語, 国内誌[査読有り]研究論文（学術雑誌）
- Since Kelly and Wendel [Arch Ophthalmol 1991;109:654-659] first reported successfully treating macular holes (MHs) using pars plana vitrectomy in 1991, MH surgery has been constantly improved. For example, introducing the removal of the internal limiting membrane considerably increased the closure rate of MHs, and the advent of microincision vitrectomy surgery reduced surgical trauma and decreased patient discomfort after surgery. As modern MH surgery can achieve a higher anatomical success rate and alleviate patients' postoperative distress, postoperative visual outcomes have lately become the primary concern. Informing patients of the expected visual acuity and visual improvement before surgery is ideal, but predicting postoperative visual outcomes is difficult because a large number of factors are associated with them. In this paper, we review previous studies and provide accumulating evidence for the relationship between individual prognostic factors and visual outcomes after MH surgery.2014年, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde, 231(3) (3), 125 - 32, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- PURPOSE: To investigate the incidence of and risk factors for a dissociated optic nerve fiber layer (DONFL) appearance after pars plana vitrectomy (PPV). METHODS: We retrospectively reviewed 189 eyes that underwent PPV with internal limiting membrane removal and judged the presence/absence of an apparent DONFL based on en face layer images produced by spectral-domain optical coherence tomography (SD-OCT). RESULTS: An apparent DONFL was observed in 47 (24.9%) eyes. The incidence of an apparent DONFL was significantly higher in the macular hole (MH) group (76.5%) than in the non-MH group (epiretinal membrane, diabetic macular edema, retinal vein occlusion, and others; 4.9%; p < 0.001). In the logistic regression analysis, surgical indication for MH was identified as the most significant DONFL risk factor (odds ratio 63.7; p = 1.05 × 10(-8)). CONCLUSION: Postoperative OCT en face layer imaging clarified that MH eyes are liable to have an apparent DONFL following PPV.2014年, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde, 232(3) (3), 170 - 8, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (公財)臨床薬理研究振興財団, 2013年06月, 臨床薬理の進歩, (34) (34), 86 - 92, 日本語近視性脈絡膜血管新生に対するビスフォスフォネート薬内服の2年後効果の検討
- PURPOSE: To investigate the effects of reproducibility of optical coherence tomography (OCT) measurements and imaging alignment on predictive performance for visual outcome following macular hole (MH) surgery. METHODS: We retrospectively reviewed 50 eyes that underwent MH surgery. Preoperative cross-sectional images through the center of the MH (on-center image) and through an off-center point (off-center image) were obtained from the OCT data. In each image, the following OCT parameters were either measured or calculated: minimum diameter, base diameter, hole height, temporal and nasal arm length, photoreceptor inner segment/outer segment (IS/OS) defect length, the hole form factor, the macular hole index and the tractional hole index. The IS/OS defect area was also measured. RESULTS: The reproducibility of OCT parameter values was moderate to high, and there was a significant difference in the mean measurement values between the on- and off-center images. Predictive values varied between sessions and raters, and only the preoperative photoreceptor IS/OS defect length consistently showed significant correlation with postoperative visual outcome. CONCLUSIONS: Both the reproducibility and imaging alignment might affect the predictive performance of the OCT parameter for postoperative visual outcome following MH surgery. The preoperative photoreceptor IS/OS defect length seems to be the most useful parameter in this regard.2013年05月, Japanese journal of ophthalmology, 57(3) (3), 308 - 15, 英語, 国内誌[査読有り]研究論文（学術雑誌）
- BACKGROUND: The effects of intravitreal ranibizumab (IVR) against exudative age-related macular degeneration (AMD) may be different associated with the lesion phenotype. This study was conducted to compare the outcomes of IVR between two different phenotypes of exudative AMD: typical neovascular AMD (tAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: This is a retrospective cohort study of 54 eyes from 54 subfoveal exudative AMD patients (tAMD 24, PCV 30 eyes). Three consecutive IVR treatments (0.5 mg) were performed every month, followed by re-injections as needed. Change in the best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were then compared between the tAMD and PCV groups over 12 months of follow-up. RESULTS: The mean BCVA was significantly improved (-0.11 logMAR units) at month 3 after the initial IVR (p <0 .001, Wilcoxon signed-rank test), and was sustained up to 12 months in all AMD patients (p =0.02). In the subgroup analysis, the tAMD group showed a significant improvement in their mean BCVA (-0.06, -0.17, -0.15 and -0.16 logMAR units at 1, 3, 6 and 12 months, respectively), but there was only a slight but non-significant improvement in the PCV group. The improvement in the BCVA was significantly greater in the tAMD group than in the PCV group (p = 0.043, repeated measures ANOVA) over 12 months. Both phenotypes showed significant improvements in the CRT during 12 months after the initial IVR. CONCLUSIONS: IVR is an effective therapy for tAMD and PCV in the BCVA improvement in Japanese patients over 12 months of follow-up. The phenotype of tAMD showed a significantly better outcome with IVR than PCV in terms of BCVA improvement.2013年04月, BMC ophthalmology, 13, 10 - 10, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- PURPOSE: Multidrug resistance protein 4 (MRP4) effluxes a wide variety of endogenous compounds, including cyclic adenosine monophosphate (cAMP), and is exclusively expressed in vascular endothelial cells (ECs) of the retina. This study aimed to investigate the role of MRP4 in retinal vascular development. METHODS: The retinal vascular phenotype of Mrp4(-/-) mice was examined by whole-mount immunohistochemistry at P3, P6, and P14. The retinas from P6 pups that received an intraperitoneal injection of either solvent control or forskolin, an inducer of intracellular cAMP formation, at P4 and P5 were analyzed in terms of their vascular formation (vascular length, vascular branching, vascular density, and the number of tip cells), cell proliferation and apoptosis, and vessel stability. RESULTS: The Mrp4(-/-) mice exhibited no overt abnormalities in the development of the retinal vasculature, but retinal vascular development in the Mrp4(-/-) mice was suppressed in response to forskolin administration. There was a significant decrease in the vascular length, vascular branching, and vascular density, and inhibited tip cell formation at the vascular front. The forskolin-treated Mrp4(-/-) mice showed an increased number of Ki67-positive and cleaved caspase 3-positive ECs, a significant decrease in the amount of pericyte coverage, and a reduced number of empty sleeves. In pups exposed to hyperoxia (75% oxygen) from P7 to P12, the Mrp4(-/-) mice showed a significant increase in the unvascularized retinal area. CONCLUSIONS: Mrp4(-/-) mice exhibited suppressed retinal vascular development in response to forskolin treatment. Thus, Mrp4 might have protective roles in retinal vascular development by regulating the intracellular cAMP level.2012年12月, Investigative ophthalmology & visual science, 53(13) (13), 8029 - 35, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- 日本皮膚科学会-大阪地方会・京滋地方会, 2012年06月, 皮膚の科学, 11(3) (3), 227 - 228, 日本語弾性線維性仮性黄色腫の2例
- PURPOSE: Sweet's syndrome (SS) is a skin disorder clinically characterized by fever, neutrophilia, and painful edematous plaques that occasionally causes posterior uveitis. We present two cases of SS with panuveitis resembling Behçet's disease (BD). SUBJECTS: Two patients with panuveitis associated with SS. OBSERVATIONS: The patient in case 1 was a 57-year-old Japanese man who developed acute severe iritis with hypopyon in the left eye. Fluorescein angiography (FA) performed 1 month after treatment showed findings observed in posterior uveitis: dye leakage from the optic disc and a petaloid pattern of hyperfluorescence in the macular region. The patient in case 2 was a 64-year-old Japanese man who complained of blurred vision in his left eye. Faint flare and occasional cells were present in the left anterior chamber, 2+ cells in the anterior vitreous, and 2+ vitreous opacification in the left eye. FA demonstrated dye leakage from the optic disc and peripheral capillary vessels in both eyes. Both patients were diagnosed as having SS on the basis of fever, neutrophilia, elevated C-reactive protein, and skin biopsy results of neutrophilic infiltration without vasculitis. CONCLUSIONS: Differentiation of SS from BD based on the ocular manifestations is difficult. Ophthalmologists should bear in mind that SS can exhibit panuveitis resembling BD.2012年05月, Japanese journal of ophthalmology, 56(3) (3), 268 - 72, 英語, 国内誌[査読有り]研究論文（学術雑誌）
- 2012年04月, European Journal of Ophthalmology, 22(2) (2), 210 - 215, 英語[査読有り]研究論文（学術雑誌）
- (公財)日本眼科学会, 2012年03月, 日本眼科学会雑誌, 116(臨増) (臨増), 239 - 239, 日本語中心性漿液性脈絡網膜症におけるARMS2およびCFH多型の検討
- (公財)日本眼科学会, 2012年03月, 日本眼科学会雑誌, 116(臨増) (臨増), 331 - 331, 日本語近視性脈絡膜血管新生に対するビスフォスフォネート薬内服の中期効果
- (公財)日本眼科学会, 2012年03月, 日本眼科学会雑誌, 116(臨増) (臨増), 265 - 265, 日本語ranibizumab硝子体内投与後のAMD再発例における臨床的及び遺伝的関連因子の検討
- The association of CD36 variants with polypoidal choroidal vasculopathy compared to typical neovascular age-related macular degeneration.PURPOSE: To clarify the association of cluster of differentiation 36 (CD36) variants with polypoidal choroidal vasculopathy (PCV) and compare them with those in typical neovascular age-related macular degeneration (tAMD). METHODS: We included 349 Japanese AMD patients (210 PCV, 139 tAMD) and 198 age-matched controls. Four tag single-nucleotide polymorphisms (SNPs)-rs10499862, rs3173798, rs3211883, and rs3173800-in the CD36 region were genotyped using the TaqMan assay. Allelic and genotypic frequencies of the SNPs were tested. RESULTS: Although none of the SNPs tested were associated with PCV, the allelic frequencies of rs3173798 and rs3173800 were significantly different between PCV and tAMD patients. Genotype association analysis demonstrated different associations of these two SNPs between PCV and tAMD in the genotype model. Haplotype analysis revealed that the association of the major haplotype (T-T-T-T) at four selected SNPs in CD36 differed significantly between PCV and tAMD patients. CONCLUSIONS: The CD36 region may be associated with the difference in genetic susceptibility for PCV and tAMD.2012年, Molecular vision, 18, 121 - 7, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Positive association of CD36 gene variants with the visual outcome of photodynamic therapy in polypoidal choroidal vasculopathy.PURPOSE: To clarify the association between cluster of differentiation 36 (CD36) gene polymorphisms and the response to photodynamic therapy (PDT) in polypoidal choroidal vasculopathy (PCV). METHODS: One hundred and thirty-seven patients with PCV were enrolled. The patients were treated with PDT and followed up for more than 6 months. Retreatments were performed every 3 months as needed based on findings from angiography. Patients who showed an improvement in their best-corrected visual acuity at 6 months post-PDT were classified as PDT responders, and the others were defined as non-responders. For the 73 responders and 64 non-responders, 19 single nucleotide polymorphisms (SNPs) across the CD36 region were genotyped using the TaqMan assay. We analyzed the association between these variants and the visual outcomes of PDT. RESULTS: The allelic frequencies of the SNPs rs3211851, rs3173798, and rs3211908 showed nominally significant differences between the PDT responders and non-responders. Genotype association analysis revealed a significant association of SNP rs3173798 with the visual outcome of PDT in a dominant model. The presence of the C allele in rs3173798 was significantly associated with a poor response to PDT after multivariate logistic regression analysis with clinical pre-PDT parameters. The mean best-corrected visual acuity in the group with the TT genotype of rs3173798 was significantly improved over 12 months of follow-up after the initial PDT. CONCLUSIONS: The coding variants in CD36 are possibly associated with the visual outcome of PDT in patients with PCV.2012年, Molecular vision, 18, 2796 - 804, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- BACKGROUND: Drugs inhibiting vascular endothelial growth factor (VEGF) signaling are globally administered to suppress deregulated angiogenesis in a variety of eye diseases. However, anti-VEGF therapy potentially affects the normal functions of retinal neurons and glias which constitutively express VEGF receptor 2. Thus, it is desirable to identify novel drug targets which are exclusively expressed in endothelial cells (ECs). Here we attempted to identify an EC-specific Rho guanine nucleotide exchange factor (GEF) and evaluate its role in retinal angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: By exploiting fluorescence-activated cell sorting and microarray analyses in conjunction with in silico bioinformatics analyses, we comprehensively identified endothelial genes in angiogenic retinal vessels of postnatal mice. Of 9 RhoGEFs which were highly expressed in retinal ECs, we show that Arhgef15 acted as an EC-specific GEF to mediate VEGF-induced Cdc42 activation and potentiated RhoJ inactivation, thereby promoting actin polymerization and cell motility. Disruption of the Arhgef15 gene led to delayed extension of vascular networks and subsequent reduction of total vessel areas in postnatal mouse retinas. CONCLUSIONS/SIGNIFICANCE: Our study provides information useful to the development of new means of selectively manipulating angiogenesis without affecting homeostasis in un-targeted tissues; not only in eyes but also in various disease settings such as cancer.2012年, PloS one, 7(9) (9), e45858, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- 眼科臨床紀要会, 2011年10月, 眼科臨床紀要, 4(10) (10), 1006 - 1006, 日本語脈絡膜新生血管を合併したUnilateral retinal pigment epithelium dysgenesisの1例
- To investigate whether retinal surface imaging by Cirrus high-definition optical coherence tomography (HD-OCT) clearly depicts the development process of a dissociated optic nerve fiber layer (DONFL) appearance after macular hole (MH) surgery. We reviewed the medical records of the patients who underwent MH surgery with internal limiting membrane peeling. The cases were then selected using three principal criteria: (1) surgeries performed by the same surgeon (S. K.), (2) pre- and postoperative Cirrus HD-OCT imaging, and (3) minimal follow-up of 3 months. All cases received a complete ophthalmologic examination. The presence/absence of a DONFL appearance was determined using a retinal surface image provided by Cirrus HD-OCT. Color fundus photographs were also used for determination if available. Fifteen cases met the criteria. A DONFL appearance was identified in 11 (73%) cases during the postoperative course by retinal surface imaging. A DONFL appearance was not detected in any OCT retinal surface image within the first postoperative month, gradually became distinct between 1 and 3 months after surgery, and remained detectable thereafter in all cases but one whose DONFL appearance became less detectable at 12 months. Indentations of the innermost retinal layer became apparent on cross-sectional OCT images as a DONFL appearance developed on OCT retinal surface images. There were two cases in which the DONFL appearance was not observed on color fundus photographs but detected on OCT retinal surface images. Retinal surface imaging provided by Cirrus HD-OCT appeared to be a promising option in evaluating a DONFL appearance after MH surgery.2011年10月, International ophthalmology, 31(5) (5), 385 - 92, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (一社)日本感染症学会, 2011年03月, 感染症学雑誌, 85(2) (2), 193 - 194, 日本語末梢ルート感染にBacillus cereus眼内炎を合併した1例
- PURPOSE: The purpose of this study was to evaluate the intraocular gas dynamics after 23-gauge transconjunctival sutureless vitrectomy (TSV) as compared with 20-gauge pars plana vitrectomy (PPV). METHODS: A consecutive series of 290 eyes that experienced 20-gauge or 23-gauge vitrectomy with 25% sulfur hexafluoride (SF6) gas tamponade were retrospectively reviewed. Intraocular gas bubble size on postoperative Day 1 and Gas50, the interval to dissipate to a 50% gas fill, were evaluated. RESULTS: The mean intraocular bubble size on postoperative Day 1 was 92.0 ± 8.3% in the 20-gauge PPV cases and 83.8 ± 13.7% in the 23-gauge TSV cases (P < 0.001). The mean Gas50 was 8.6 ± 1.6 days in the 20-gauge PPV cases and 6.6 ± 2.2 days in the 23-gauge TSV cases (P < 0.001). Thorough peripheral vitrectomy and 23-gauge TSV were significantly associated with Gas50 ≤ 4 days (odds ratio, 4.62 and 16.8; P = 0.036 and P = 0.007, respectively). Among thoroughly vitrectomized eyes, 13 eyes treated with 23-gauge PPV with intraoperative suture placement at the sclerotomy sites had gas longevity comparative to those with 20-gauge PPV. CONCLUSION: Eyes treated with 23-gauge TSV tend to have earlier gas disappearance or incomplete gas fill. Intraoperative suture placement would be a solution.2011年02月, Retina (Philadelphia, Pa.), 31(2) (2), 250 - 6, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- PURPOSE: To evaluate the retinal toxicity of intravitreal tissue plasminogen activator (tPA) injection for branch and central retinal vein occlusion (BRVO and CRVO) using the electroretinogram (ERG). PROCEDURES: Ten BRVO patients and 5 CRVO patients were enrolled. A complete examination including full-field ERG, visual acuity, central retinal thickness (CRT), and evaluation of systemic and ocular complications was performed before and after intravitreal tPA injection. RESULTS: No significant differences were found in the amplitude or implicit time of any ERG component after tPA injection, and no systemic or ocular complication was observed. The improvement of visual acuity was significant at month 3 in the BRVO group (p < 0.05) but not in the CRVO group. CRT significantly decreased over the course of 3 months in both groups (p < 0.01). CONCLUSION: Intravitreal tPA injection seems to be a safe and effective treatment option for macular oedema caused by retinal vein occlusions.2011年, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde, 226(2) (2), 81 - 6, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Purpose. To evaluate the early response to intravitreal ranibizumab (IVR) in two different phenotypes of age-related macular degenerations (AMD): typical neovascular AMD (tAMD) and polypoidal choroidal vasculopathy (PCV). Methods. Sixty eyes from 60 patients (tAMD 28, PCV 32 eyes) were recruited. Three consecutive IVR treatments (0.5 mg) were performed every month. Change in the best-corrected visual acuity (BCVA) and central retinal thickness (CRT) was then compared between the tAMD and PCV groups. Results. The mean BCVA logMAR was significantly improved at month 1 and month 3 after the initial IVR in the tAMD group, but there was no change in the PCV group. Both phenotypes showed significant improvements in the CRT during the 3 months after the initial IVR. There were no significant differences in the improvements of the CRT in the tAMD versus the PCV group. In the stepwise analysis, a worse pretreatment BCVA and tAMD lesions were significantly beneficial for a greater improvement of BCVA at 3 months after the initial IVR. Conclusions. The phenotype of tAMD showed a significantly better early response to IVR than PCV in terms of BCVA improvement.2011年, Journal of ophthalmology, 2011, 742020 - 742020, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Difference between age-related macular degeneration and polypoidal choroidal vasculopathy in the hereditary contribution of the A69S variant of the age-related maculopathy susceptibility 2 gene (ARMS2).PURPOSE: To investigate whether the A69S variant of the age-related maculopathy susceptibility 2 gene (ARMS2) has a different hereditary contribution in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). METHODS: We initially conducted a comparative genetic analysis of neovascular AMD and PCV, genotyping the ARMS2 A69S variant in 181 subjects with neovascular AMD, 198 subjects with PCV, and 203 controls in a Japanese population. Genotyping was conducted using TaqMan technology. Results were then integrated into a meta-analysis of previous studies representing an assessment of the association between the ARMS2 A69S variant and neovascular AMD and/or PCV, comprising a total of 3,828 subjects of Asian descent. The Q-statistic test was used to assess between-study heterogeneity. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a fixed effects model. RESULTS: The genetic effect of the A69S variant was stronger in neovascular AMD (allelic summary OR=3.09 [95% CI, 2.71-3.51], fixed effects p<0.001) than in PCV (allelic summary OR=2.13 [95% CI, 1.91-2.38], fixed effects p<0.001). The pooled risk allele frequency was significantly higher in neovascular AMD (64.7%) than in PCV (55.6%). The population attributable risks for the variant allele were estimated to be 43.9% (95% CI, 39.0%-48.4%) and 29.7% (95% CI, 25.4%-34.0%) for neovascular AMD and PCV, respectively. No significant between-study heterogeneity was observed in any statistical analysis in this meta-analysis. CONCLUSIONS: Our meta-analysis provides substantial evidence that the ARMS2 A69S variant confers a significantly higher risk of neovascular AMD than PCV. Furthermore, there is compelling evidence that the risk attributable to the A69S variant differs between geographic atrophy and neovascular AMD. Together with defining the molecular basis of susceptibility, understanding the relationships between this genomic region and disease subtypes will yield important insights, elucidating the biologic architecture of this phenotypically heterogeneous disorder.2011年, Molecular vision, 17, 3574 - 82, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- BACKGROUND: Genetic variants in the complement component 3 gene (C3) have been shown to be associated with age-related macular degeneration (AMD) in Caucasian populations of European descent. In particular, a nonsynonymous coding variant, rs2230199 (R102G), is presumed to be the most likely causal variant in the C3 locus based on strong statistical evidence for disease association and mechanistic functional evidence. However, the risk allele is absent or rare (<1%) in Japanese and Chinese populations, and the association of R102G with AMD has not been reported in Asian populations. Genetic heterogeneity of disease-associated variants among different ethnicities is common in complex diseases. Here, we sought to examine whether other common variants in C3 are associated with wet AMD, a common advanced-stage manifestation of AMD, in a Japanese population. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped 13 tag single nucleotide polymorphisms (SNPs) that capture the majority of common variations in the C3 locus and tested for associations between these SNPs and wet AMD in a Japanese population comprising 420 case subjects and 197 controls. A noncoding variant in C3 (rs2241394) exhibited statistically significant evidence of association (allelic P = 8.32 × 10(-4); odds ratio = 0.48 [95% CI = 0.31-0.74] for the rs2241394 C allele). Multilocus logistic regression analysis confirmed that the effect of rs2241394 was independent of the previously described loci at ARMS2 and CFH, and that the model including variants in ARMS2 and CFH plus C3 rs2241394 provided a better fit than the model without rs2241394. We found no evidence of epistasis between variants in C3 and CFH, despite the fact that they are involved in the same biological pathway. CONCLUSIONS: Our study provides evidence that C3 is a common AMD-associated locus that transcends racial boundaries and provides an impetus for more detailed genetic characterization of the C3 locus in Asian populations.2011年, PloS one, 6(12) (12), e28847, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- 眼科臨床紀要会, 2010年10月, 眼科臨床紀要, 3(10) (10), 994 - 994, 日本語生理的・病的網膜血管新生におけるABCトランスポーターの発現
- 眼科臨床紀要会, 2010年10月, 眼科臨床紀要, 3(10) (10), 1024 - 1025, 日本語悪性腫瘍随伴網膜症に対するトリアムシノロンテノン嚢下注射にて失明を回避し得た一例
- The multidrug resistance protein (MRP) MRP4/ABCC4 is an ATP-binding cassette transporter that actively effluxes endogenous and xenobiotic substrates out of cells. In the rodent retina, Mrp4 mRNA and protein are exclusively expressed in vascular endothelial cells, but the angiogenic properties of Mrp4 are poorly understood so far. This study aims to explore the angiogenic properties of MRP4 in human retinal microvascular endothelial cells (HRECs) utilizing the RNA interference (RNAi) technique. MRP4 expression was decreased at the mRNA and protein levels after stimulation with exogenous vascular endothelial growth factor in a dose-dependent manner. RNAi-mediated MRP4 knockdown in HRECs do not affect cell proliferation but enhances cell migration. Moreover, cell apoptosis induced by serum starvation was less prominent in MRP4 siRNA-treated HRECs as compared to control siRNA-treated HRECs. In a Matrigel-based tube-formation assay, although MRP4 knockdown did not lead to a significant change in the total tube length, MRP4 siRNA-treated HRECs assembled and aggregated into a massive tube-like structure, which was not observed in control siRNA-treated HRECs. These results suggest that MRP4 is uniquely involved in retinal angiogenesis.2010年10月, Biochemical and biophysical research communications, 400(4) (4), 593 - 8, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- A Case of Bilateral Macular Holes Showing Onset and Spontaneous Closure over Very Short Intervals.PURPOSE: Idiopathic macular holes (MHs) may occur bilaterally, and the spontaneous closure of MHs was documented previously. The median interval between the onset of MHs in each eye was reported to be 17.5 months. METHOD: We report a case of bilateral MHs which occurred and resolved spontaneously over a very short interval. RESULTS: A 48-year-old woman with no history of ocular disease complained of a central scotoma and metamorphopsia in the left eye. Stage 1A MH was diagnosed in the left eye on the initial visit, which resolved spontaneously with vitreofoveal separation after 1 month. After an additional month, she complained of a similar visual disturbance in the right eye. Stage 1B MH was found in the right eye, which showed spontaneous closure after 1 month in the same manner as the left eye. CONCLUSION: We present a unique case of bilateral MHs which occurred and resolved spontaneously within a very short time period. Careful observation of the non-involved eye is needed to address the risk of early onset bilateral MHs.2010年09月, Case reports in ophthalmology, 1(2) (2), 47 - 52, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- 金原出版(株), 2010年07月, 眼科, 52(7) (7), 964 - 964, 日本語Cirrus OCTによって黄斑円孔術後DONFLの発生過程を観察できた症例
- 2010年04月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 51(13) (13)Knockdown of Multidrug Resistance-Associated Protein 4 by Sima Enhances Cell Migration and Tube Formation in Human Retinal Endothelial Cells[査読有り]研究論文（学術雑誌）
- (公財)日本眼科学会, 2010年03月, 日本眼科学会雑誌, 114(臨増) (臨増), 320 - 320, 日本語中心性漿液性脈絡網膜症眼の白内障術後に視神経乳頭に連続した網膜分離症が生じた1例
- (公財)日本眼科学会, 2010年03月, 日本眼科学会雑誌, 114(臨増) (臨増), 208 - 208, 日本語ポリープ状脈絡膜血管症に対する光線力学的療法における抗凝固薬内服の影響
- Purpose. Choroidal neovascularization (CNV) is often associated with age-related macular degeneration (AMD) and pathological myopia (PM). Bisphosphonates, the drug of choice to treat osteoporosis, have been recently reported to have anti-angiogenic effects. The purpose of this study is to investigate the therapeutic effects of oral bisphosphonates for CNV in humans. Methods. Thirty-six consecutive cases with CNV due to AMD or PM who declined anti-VEGF therapy were recruited. The patients were prescribed 5 mg of oral alendronates daily for 6 months. The best-corrected visual-acuity (BCVA), the lesion size in fundus photographs and fluorescein angiography, foveal thickness and total macular volume in optical coherence tomography were compared between pre- and post-treatment. Results. The mean BCVA of the patients was significantly improved after a months with the treatment in the AMD group. In the PM group, the mean BCVA was maintained up to 6 months with the treatment. The mean lesion size was significantly decreased by 3 months in both groups. The averages of foveal thickness and total macular volume were significantly reduced after 1 month of treatment in the AMD group.Conclusions. Oral bisphosphonate should be further investigated as a possible therapeutic and preventive drug for CNV due to AMD and PM.2010年, Journal of ophthalmology, 2010, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- ATP-binding cassette (ABC) transporters at the blood-brain barrier (BBB) are responsible for the majority of the transcellular movement of various substrates, including various drugs, and contribute to the maintenance of brain homeostasis. Clinically, the abnormal expression of efflux transporters at the BBB is known to be associated with brain diseases such as epilepsy. In the retina, vascular endothelial cells outline the inner blood-retinal barrier (BRB) like the BBB, and some ABC efflux transporters are expressed in the adult retina. However, little is known about ABC transporter expression during retinal development or under pathological conditions. Here, we examined ABC transporter expression in the mouse retina, and demonstrated that P-glycoprotein (P-gp)/ABCB1, Mrp4/ABCC4, and Bcrp/ABCG2 were almost uniformly expressed in these blood vessels, including the capillaries and large vessels. This expression persisted throughout the developmental period, and the hyaloid vessels that normally feed the developing eye were immunoreactive for P-gp and Mrp4. Furthermore, we investigated ABC transporter expression in pathological angiogenesis using an oxygen-induced retinopathy model where hypoxia-induced preretinal neovascularization occurred around the central avascular retina. P-gp was prominently immunoexpressed but Mrp4 and Bcrp were weakly immunoexpressed, in the preretinal neovascular tufts. These findings will be helpful for understanding the roles of ABC transporters during both physiological and pathological retinal angiogenesis, and might provide new insights for safe and effective drug administration to infants or patients with angiogenic ocular disease.2009年08月, Brain research, 1283, 186 - 93, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- 2009年01月, ARCHIVES OF OPHTHALMOLOGY, 127(1) (1), 105 - 107, 英語Serous Macular Detachment Due to Diabetic Papillopathy Detected Using Optical Coherence Tomography[査読有り]研究論文（学術雑誌）
- 金原出版(株), 2008年12月, 眼科, 50(13) (13), 1985 - 1985, 日本語副腎皮質ステロイドパルス療法が著効したAZOORの1例
- 金原出版(株), 2008年12月, 眼科, 50(13) (13), 1986 - 1986, 日本語ヘルペス性虹彩毛様体炎に網膜病変を伴った1症例
- PURPOSE: To report a case of familial exudative vitreoretinopathy (FEVR) rapidly resolved by intravitreal injection of bevacizumab. METHODS: A 36-year-old woman complained about floaters and visual field defect. Funduscopic examinations revealed retinal vessel anastomosis located between the equator and ora serrata in both eyes. The right eye was accompanied with slight vitreous hemorrhage. Since the patient declined retinal cryopexy for cosmetic reasons, intravitreal bevacizumab injections (1.25 mg/0.05 ml) were performed in both eyes. RESULTS: Treatment resulted in the rapid regression and the accelerated fibrosis of neovascular tissues. At 4-month follow-up in the right eye and 1-month follow-up in the left, no signs of systemic or ocular complications were detected. CONCLUSIONS: Intravitreal injection of bevacizumab may be considered as an alternative method in treating FEVR.2008年12月, Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 246(12) (12), 1787 - 9, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- 2008年10月, BRITISH JOURNAL OF OPHTHALMOLOGY, 92(10) (10), 1433 - 1434, 英語研究論文（学術雑誌）
- 2008年09月, BRITISH JOURNAL OF OPHTHALMOLOGY, 92(9) (9), 1261 - 1264, 英語研究論文（学術雑誌）
- 2008年09月, EYE, 22(9) (9), 1154 - 1160, 英語[査読有り]研究論文（学術雑誌）
- 眼科臨床医報会, 2007年11月, 眼科臨床医報, 101(11) (11), 1135 - 1135, 日本語Unilateral acute idiopathic maculopathyの1例
- 眼科臨床医報会, 2006年10月, 眼科臨床医報, 100(10) (10), 809 - 809, 日本語Dissociated optic nerve fiber layer眼における視機能、網膜神経線維層厚の評価
- 2006年08月, EYE, 20(8) (8), 882 - 887, 英語[査読有り]研究論文（学術雑誌）
- Angiogenesis in the mouse retina: a model system for experimental manipulation.The vascular system of the mouse retina provides a useful model for analyzing the molecular and cellular mechanisms regulating angiogenesis because (1) hierarchical vascular networks are newly formed only after birth, (2) the cellular components involved in angiogenesis are well characterized, and (3) all the processes are accessible for monitoring and manipulation. In this article, we present an overview of our current understanding of the process of retinal angiogenesis and describe a number of methodologies applicable to experimental manipulation of the retinal vascular system.2006年03月, Experimental cell research, 312(5) (5), 676 - 83, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Tlx acts as a proangiogenic switch by regulating extracellular assembly of fibronectin matrices in retinal astrocytes.In response to hypoxia, hypoxia-inducible factors act as the primary proangiogenic triggers by regulating transcription levels of target genes, including VEGF. However, little is known about the specific factors that control other components of the angiogenic process, particularly formation of matrix scaffolds that promote adhesion and migration of endothelial cells. We show that in the postnatal mouse retina, the orphan nuclear receptor tailless (Tlx) is strongly expressed in the proangiogenic astrocytes, which secrete VEGF and fibronectin. Tlx expression by retinal astrocytes is controlled by oxygen concentration and rapidly downregulated upon contact with blood vessels. In mice null for Tlx, retinal astrocytes maintain VEGF expression; however, the extracellular assembly of fibronectin matrices by astrocytes is severely impaired, leading to defective scaffold formation and a complete failure of normal retinal vascular development. This work identifies Tlx as an essential component of the molecular network involved in the hypoxia-inducible proangiogenic switch in retinal astrocytes.2006年02月, The Journal of clinical investigation, 116(2) (2), 369 - 77, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- 眼科臨床医報会, 2005年08月, 眼科臨床医報, 99(8) (8), 686 - 686, 日本語黄斑浮腫に対するトリアムシノロン後部テノン嚢下注射の治療成績
- 2005年07月, Japanese Journal of Ophthalmology, 49(4) (4), 294 - 296, 英語[査読有り]研究論文（学術雑誌）
- A case of POEMS syndrome with cystoid macular edema.PURPOSE: To introduce a case of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome with bilateral cystoid macular edema (CME). DESIGN: Interventional case report. METHODS: Temporal changes of serum vascular endothelial growth factor (VEGF) levels and macular thickness were evaluated. RESULTS: A 53-year-old woman with POEMS syndrome was referred complaining of long-standing impaired vision. Typical CME demonstrating petal-like dye pooling was observed in both eyes. After subtenon administrations of triamcinolone acetonide (TA), pars plana vitrectomy, and intraocular TA injection in the right eye, macular thickness decreased. Intraocular VEGF levels were <31 pg/ml at the vitrectomy and intraocular TA injection, whereas serum the VEGF level was >2000 pg/ml throughout the follow-up periods. In the untreated left eye, macular thickness altered related to serum VEGF level. CONCLUSIONS: Based on the low intraocular VEGF level and serum VEGF-related change of macular thickness, elevated serum VEGF might be a cause of CME in POEMS syndrome.2005年03月, American journal of ophthalmology, 139(3) (3), 563 - 6, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- 眼科臨床医報会, 2005年03月, 眼科臨床医報, 99(3) (3), 231 - 233, 日本語小児白内障術後の近見・遠見視力発達
- 2005年02月, EYE, 19(2) (2), 235 - 237, 英語[査読有り]研究論文（学術雑誌）
- 2005年01月, Japanese Journal of Ophthalmology, 49(1) (1), 65 - 67, 英語[査読有り]研究論文（学術雑誌）
- Optical coherence tomography detects characteristic retinal nerve fiber layer thickness corresponding to band atrophy of the optic discs.OBJECTIVES: To analyze retinal nerve fiber layer (RNFL) thickness in eyes with band atrophy by use of optical coherence tomography (OCT) and to evaluate the ability of OCT to detect this characteristic pattern of RNFL loss. DESIGN: Cross-sectional, retrospective study. PARTICIPANTS: Thirty-four eyes of 18 patients with bitemporal hemianopia caused by optic chiasm compression by chiasmal tumors were studied. All eyes were divided into 3 groups according to visual field loss grading after Goldmann perimetry. INTERVENTIONS: Retinal nerve fiber layer thickness measurements with OCT. MAIN OUTCOME MEASURES: Retinal nerve fiber layer thickness around the optic disc was measured by OCT (3.4-mm diameter circle). Calculation of the changes in OCT parameters, including the horizontal (nasal + temporal quadrant RNFL thickness) and vertical values (superior + inferior quadrant RNFL thickness) was based on data from 160 normal eyes. Comparison between the 3 visual field grading groups was done with the analysis of variance test. The receiver operating characteristic (ROC) curve for the horizontal and vertical value were calculated, and the areas under the curve (AUC) were compared. RESULTS: Retinal nerve fiber layer thickness in eyes with band atrophy decreased in all OCT parameters. The reduction rate in average and temporal RNFL thickness and horizontal value was correlated with visual field grading. The AUC of horizontal value was 0.970+/-0.011, which was significantly different from AUC of vertical value (0.903+/-0.022). CONCLUSIONS: The degree of RNFL thickness reduction correlated with that of visual field defects. Optical coherence tomography was able to identify the characteristic pattern of RNFL loss in these eyes.2004年12月, Ophthalmology, 111(12) (12), 2278 - 83, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Prediction of postoperative visual outcome based on hole configuration by optical coherence tomography in eyes with idiopathic macular holes.PURPOSE: To evaluate whether an index based on hole configuration can be used to predict visual outcome in eyes with idiopathic macular holes. DESIGN: Prospective interventional case series. METHODS: Thirty-five eyes of 32 patients with idiopathic stage 2 or 3 macular hole were enrolled in this study. The best-corrected visual acuity (BCVA), cross-sectional image of the macular hole by optical coherence tomography (OCT), and retinal thickness in the central (<1000 microm), inner (1000 to 2220 microm), and outer ring areas (2220 to 3450 microm) as defined by the OCT retinal mapping program were evaluated preoperatively and at 1, 3, 6, and 12 months postoperatively. The change in retinal thickness of the inner ring area at the 6-month postoperative period was used to evaluate the degree of preoperative retinal deformation. The macular hole index (MHI) (ratio of hole height to base diameter of hole) was calculated and correlated with minimum diameter of hole, base diameter of hole, the postoperative decrease in macular thickness, and the postoperative BCVA. The postoperative BCVA was further evaluated in two patient-matched groups. RESULTS: Retinal thickness values in the inner ring area were decreased at the 1-month postoperative period. MHI significantly correlated with the postoperative decrease in macular thickness in the inner ring area at 6 months (correlation coefficient = -0.632, P = .030, Spearman analysis) and with the postoperative BCVA (P = .013, multiple regression analysis). Postoperative BCVA in the MHI >/=0.5 group was better than that in the MHI <0.5 group (P = .032, Mann-Whitney test). CONCLUSIONS: The MHI is a ratio easily calculated from OCT transverse images of the macular area. The MHI represents the preoperative configuration of a macular hole and is a prognostic factor for visual outcome.2004年11月, American journal of ophthalmology, 138(5) (5), 709 - 16, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- 眼科臨床医報会, 2004年11月, 眼科臨床医報, 98(11) (11), 1040 - 1040, 日本語白点が自然消退した黄斑変性を伴う眼底白点症の1例
- 眼科臨床医報会, 2004年11月, 眼科臨床医報, 98(11) (11), 1047 - 1047, 日本語内境界膜剥離を併用した黄斑円孔術後の網膜神経線維層厚の変化
- 日本神経眼科学会, 2004年10月, 神経眼科, 21(増補1) (増補1), 89 - 89, 日本語相対的求心性瞳孔障害と光干渉断層計で測定した網膜神経線維層厚の関係
- 日本眼科紀要会, 2004年10月, 日本眼科紀要, 55(10) (10), 801 - 803, 日本語M-CHARTS TMによる黄斑上膜と中心性漿液性脈絡網膜症の変視量の検討
- 2004年03月, Japanese Journal of Ophthalmology, 48(2) (2), 106 - 114, 英語[査読有り]研究論文（学術雑誌）
- 眼科臨床医報会, 2004年01月, 眼科臨床医報, 98(1) (1), 53 - 53, 日本語白点が自然消退した眼底白点症の1例
- 眼科臨床医報会, 2004年01月, 眼科臨床医報, 98(1) (1), 52 - 52, 日本語黄斑疾患における定量的形態解析
- 眼科臨床医報会, 2003年11月, 眼科臨床医報, 97(11) (11), 1010 - 1010, 日本語網膜分離に伴った黄斑円孔の1例
- 眼科臨床医報会, 2003年11月, 眼科臨床医報, 97(11) (11), 1025 - 1026, 日本語網膜内層にまで障害が及んだacute zonal occult outer retinopathyの1例
- 眼科臨床医報会, 2003年11月, 眼科臨床医報, 97(11) (11), 1004 - 1004, 日本語光干渉断層計を用いた黄斑円孔術後の網膜厚変化の評価
- 眼科臨床医報会, 2003年11月, 眼科臨床医報, 97(11) (11), 1019 - 1019, 日本語形態的に著明な構造異常を呈しながら視力が良好に保たれている特発性嚢胞様黄斑浮腫
- A novel RDH5 gene mutation in a patient with fundus albipunctatus presenting with macular atrophy and fading white dots.PURPOSE: To report a novel homozygous RDH5 gene mutation in a 76-year-old fundus albipunctatus who developed macular atrophy with the disappearance of white dots. DESIGN: Observational case report. METHODS: Direct genomic sequencing for RDH5 mutations was done after complete ophthalmic examination. RESULTS: Fundoscopy revealed only macular atrophy with notable absence of white dots. A homozygous G490T (Val164Phe) missense RDH5 gene mutation was detected. CONCLUSIONS: This is the first reported long-term case of fundus albipunctatus demonstrating macular atrophy with fading of the typical white dots. Gene studies may be the only method for distinguishing fundus albipunctatus from other types of macular atrophy in the elderly.2003年09月, American journal of ophthalmology, 136(3) (3), 572 - 4, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- 眼科臨床医報会, 2003年06月, 眼科臨床医報, 97(6) (6), 500 - 500, 日本語ILM peeling後の網膜神経線維厚の変化
- 2003年, PROGRESS IN STRABISMOLOGY, 125 - 128, 英語A case of bilateral congenital superior oblique palsy developing after trauma[査読有り]研究論文（国際会議プロシーディングス）
- (公財)日本眼科学会, 2021年03月, 日本眼科学会雑誌, 125(臨増) (臨増), 170 - 170, 日本語日本におけるPRPH2関連網膜ジストロフィの実態
- (株)医学書院, 2020年02月, 臨床眼科, 74(2) (2), 216 - 220, 日本語眼炎症外来の事件簿(Case18) 緩徐に進行する中心視野異常を自覚する50代女性
- (株)北隆館, 2020年02月, Precision Medicine, 3(2) (2), 155 - 160, 日本語研究者の最新動向 ぶどう膜炎続発緑内障に対する低侵襲手術
- Dove Medical Press Ltd, 2020年, Clinical Ophthalmology, 14, 1229 - 1236, 英語書評論文,書評,文献紹介等
- 2020年, 日本網膜硝子体学会総会プログラム・講演抄録集, 59th網膜中心静脈閉塞の初診時視力に影響を及ぼす因子-多施設後ろ向き研究-
- 眼科臨床紀要会, 2019年11月, 眼科臨床紀要, 12(11) (11), 834 - 834, 日本語滲出型加齢黄斑変性の固視に関する検討
- 眼科臨床紀要会, 2019年11月, 眼科臨床紀要, 12(11) (11), 854 - 854, 日本語TREX1遺伝子変異に伴うretinal vasculopathy with cerebral leukoencephalopathyの1例
- 日本視能矯正学会, 2019年11月, 日本視能矯正学会プログラム抄録集, 60回, 89 - 89, 日本語視力良好な中心性漿液性脈絡網膜症における治療後不等像視の関連因子についての検討
- (株)医学書院, 2019年10月, 臨床眼科, 73(11) (11), 31 - 38, 日本語【実戦 メディカル眼科治療アップデート】メディカル眼科治療 薬物療法の基本と留意点 眼疾患における生物学的製剤の最近の動向
- (株)メディカ出版, 2019年10月, 眼科グラフィック, 8(5) (5), 592 - 599, 日本語【ぶどう膜炎の治療アップデート】ぶどう膜炎外科治療2019
- (株)先端医学社, 2019年10月, Retina Medicine, 8(2) (2), 139 - 144, 日本語【慢性疾患 治療の着地点〜さじ加減と落としどころ〜】サルコイドーシス(2)
- 日本臨床免疫学会, 2019年10月, 日本臨床免疫学会総会プログラム・抄録集, 47回, 126 - 126, 日本語非感染性ぶどう膜炎におけるアダリムマブ治療前後の鎮静化状態の達成とその臨床的意義
- 眼科臨床紀要会, 2019年10月, 眼科臨床紀要, 12(10) (10), 769 - 769, 日本語En face slab OCT像を用いた網膜静脈分枝閉塞症の乳頭黄斑線維束障害についての検討
- (一社)日本糖尿病合併症学会, 2019年09月, 糖尿病合併症, 33(Suppl.1) (Suppl.1), 169 - 169, 日本語局所ステロイドは血糖に影響を与えない?
- (一社)日本糖尿病合併症学会, 2019年09月, 糖尿病合併症, 33(Suppl.1) (Suppl.1), 270 - 270, 日本語視力良好な糖尿病黄斑浮腫に対する抗VEGF薬硝子体注射の12ヵ月治療成績
- 金原出版(株), 2019年09月, 眼科, 61(10) (10), 1249 - 1254, 日本語【眼科と薬剤】(第2部)薬物治療の副作用 眼科で使用する免疫抑制薬(シクロスポリン)の副作用
- 眼科臨床紀要会, 2019年08月, 眼科臨床紀要, 12(8) (8), 648 - 648, 日本語下垂体茎断裂症候群に対するホルモン治療中に進行性の網膜変性症の合併を認めた1症例
- 金原出版(株), 2019年08月, 眼科, 61(8) (8), 821 - 826, 日本語【感染性眼疾患に対する外科的治療】感染性ぶどう膜炎
- (一社)日本糖尿病合併症学会, 2019年06月, 糖尿病合併症, 33(1) (1), 27 - 27, 日本語全身加療と局所変化 全身加療と糖尿病網膜神経変性
- (株)全日本病院出版会, 2019年04月, OCULISTA, (73) (73), 47 - 54, 日本語【これでわかる自己免疫性眼疾患】自己免疫疾患・膠原病に随伴するぶどう膜炎
- (公財)日本眼科学会, 2019年03月, 日本眼科学会雑誌, 123(3) (3), 312 - 336, 日本語生体イメージングと眼病理 統合的アプローチによる糖尿病網膜症研究の新展開
- (公財)日本眼科学会, 2019年03月, 日本眼科学会雑誌, 123(臨増) (臨増), 213 - 213, 日本語網膜静脈分枝閉塞症に伴う黄斑浮腫における網膜最内層/内層/外層障害と視力予後の評価
- (公財)日本眼科学会, 2019年03月, 日本眼科学会雑誌, 123(臨増) (臨増), 216 - 216, 日本語糖尿病性黄斑浮腫に対する12ヵ月のアフリベルセプト治療成績に影響する因子の検討
- (公財)日本眼科学会, 2019年03月, 日本眼科学会雑誌, 123(臨増) (臨増), 224 - 224, 日本語Vogt-小柳-原田病治療経過中の脈絡膜再肥厚と脈絡膜構造変化の検討
- (公財)日本眼科学会, 2019年03月, 日本眼科学会雑誌, 123(臨増) (臨増), 273 - 273, 日本語Vogt-小柳-原田病治療前後の脈絡膜構造指標の変化と相関
- (公財)日本眼科学会, 2019年03月, 日本眼科学会雑誌, 123(臨増) (臨増), 289 - 289, 日本語視力良好な中心性漿液性脈絡網膜症における治療後歪視の予測因子についての検討
- 金原出版(株), 2019年03月, 眼科, 61(3) (3), 289 - 293, 日本語網膜橋渡し研究アップデート 神経保護記事・総説・解説・論説等（学術雑誌）
- (株)メディカル葵出版, 2019年01月, あたらしい眼科, 36(1) (1), 35 - 42, 日本語【全身疾患と眼:新しい疾患概念による眼科診療の新展開】強直性脊椎炎関連記事・総説・解説・論説等（学術雑誌）
- エーザイ(株), 2018年10月, クリニシアン, 65(10) (10), 912 - 917, 日本語【Immunology〜領域を超えた挑戦〜】Uve領域 非感染性ぶどう膜炎患者の治療を考える トータルマネジメントについて記事・総説・解説・論説等（学術雑誌）
- (株)医学書院, 2018年10月, 臨床眼科, 72(11) (11), 299 - 302, 日本語【7年前の常識は現在の非常識!-眼科診療の最新標準】ぶどう膜炎・強膜炎・感染症 ぶどう膜炎・強膜炎 ステロイド製剤の局所での使い方記事・総説・解説・論説等（学術雑誌）
- Vision loss in diabetic retinopathy (DR) is ascribed primarily to retinal vascular abnormalities-including hyperpermeability, hypoperfusion, and neoangiogenesis-that eventually lead to anatomical and functional alterations in retinal neurons and glial cells. Recent advances in retinal imaging systems using optical coherence tomography technologies and pharmacological treatments using anti-vascular endothelial growth factor drugs and corticosteroids have revolutionized the clinical management of DR. However, the cellular and molecular mechanisms underlying the pathophysiology of DR are not fully determined, largely because hyperglycemic animal models only reproduce limited aspects of subclinical and early DR. Conversely, non-diabetic mouse models that represent the hallmark vascular disorders in DR, such as pericyte deficiency and retinal ischemia, have provided clues toward an understanding of the sequential events that are responsible for vision-impairing conditions. In this review, we summarize the clinical manifestations and treatment modalities of DR, discuss current and emerging concepts with regard to the pathophysiology of DR, and introduce perspectives on the development of new drugs, emphasizing the breakdown of the blood-retina barrier and retinal neovascularization.2018年10月, Diabetes & metabolism journal, 42(5) (5), 364 - 376, 英語, 国際誌[査読有り]
- 日本糖尿病眼学会, 2018年09月, 日本糖尿病眼学会誌, 22, 70 - 70, 日本語糖尿病網膜症病態解明への最新知見 遺伝子改変マウスで糖尿病網膜症を再現できるか?
- 日本糖尿病眼学会, 2018年09月, 日本糖尿病眼学会誌, 22, 134 - 134, 日本語実臨床における糖尿病黄斑浮腫に対するラニビズマブ硝子体注射の12ヵ月治療成績
- (株)メディカル葵出版, 2018年08月, あたらしい眼科, 35(8) (8), 1017 - 1024, 日本語【続発緑内障】ぶどう膜炎性緑内障記事・総説・解説・論説等（学術雑誌）
- (公財)日本眼科学会, 2018年03月, 日本眼科学会雑誌, 122(臨増) (臨増), 240 - 240, 日本語実臨床における糖尿病黄斑浮腫治療の実態 VEGF阻害薬治療
- (公財)日本眼科学会, 2018年03月, 日本眼科学会雑誌, 122(臨増) (臨増), 240 - 240, 日本語実臨床における糖尿病黄斑浮腫治療の実態 介入治療開始年度比較
- 2018年, 日本眼感染症学会・日本眼炎症学会・日本コンタクトレンズ学会総会・日本涙道・涙液学会プログラム・講演抄録集, 55th-52nd-61st-7th, 97, 日本語3歳女児に生じたVogt‐小柳‐原田病疑い症例
- (一社)日本糖尿病合併症学会, 2017年10月, 糖尿病合併症, 31(Suppl.1) (Suppl.1), 349 - 349, 日本語糖尿病性黄斑浮腫に対するアフリベルセプト治療に影響する因子についての検討
- (株)メディカル葵出版, 2017年08月, あたらしい眼科, 34(8) (8), 1091 - 1096, 日本語【見逃したくない眼部悪性腫瘍-部位別の診断と治療-】治らないぶどう膜炎 仮面症候群記事・総説・解説・論説等（その他）
- 日本糖尿病眼学会, 2017年04月, 日本糖尿病眼学会誌, 21, 138 - 138, 日本語糖尿病黄斑浮腫に対するラニビズマブ硝子体注射の6ヵ月治療成績
- (公財)日本眼科学会, 2017年03月, 日本眼科学会雑誌, 121(臨増) (臨増), 167 - 167, 英語近視関連WNT7B変異の同定による近視発症機序への洞察(WNT7B polymorphism and the mechanism underlying the development of myopia)
- (公財)日本眼科学会, 2017年03月, 日本眼科学会雑誌, 121(臨増) (臨増), 323 - 323, 日本語ぶどう膜炎に伴う高眼圧・緑内障に対する術野展開用鈎を用いた線維柱帯切除術の効果会議報告等
- 眼科臨床紀要会, 2016年11月, 眼科臨床紀要, 9(11) (11), 916 - 916, 日本語OCT angiographyを用いた脈絡膜新生血管検出率
- 眼科臨床紀要会, 2016年11月, 眼科臨床紀要, 9(11) (11), 920 - 920, 日本語網膜静脈分枝閉塞症に伴う黄斑浮腫に対するラニビズマブ硝子体注射の6ヵ月治療成績
- 眼科臨床紀要会, 2016年11月, 眼科臨床紀要, 9(11) (11), 936 - 936, 日本語近視性脈絡膜血管新生に対するビスフォスフォネート内服療法の3年経過
- 眼科臨床紀要会, 2016年11月, 眼科臨床紀要, 9(11) (11), 947 - 947, 日本語視神経乳頭コロボーマ合併網膜剥離に対して硝子体手術を施行し形態学的改善を得た1例
- 2016年09月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 57(12) (12), 英語Mrp4 deficiency has no apparent effect on age-related changes of the mouse retina研究発表ペーパー・要旨（国際会議）
- 金原出版(株), 2016年09月, 眼科, 58(9) (9), 999 - 999, 日本語進化するぶどう膜炎の治療戦略
- (一社)日本糖尿病合併症学会, 2016年09月, 糖尿病合併症, 30(Suppl.1) (Suppl.1), 143 - 143, 日本語糖尿病網膜症病態解明への最新知見 遺伝子改変マウスで糖尿病網膜症を再現できるか?
- (一社)日本糖尿病合併症学会, 2016年09月, 糖尿病合併症, 30(Suppl.1) (Suppl.1), 254 - 254, 日本語実臨床における糖尿病黄斑浮腫に対するラニビズマブ硝子体注射の12ヵ月治療成績
- (一社)日本腎臓学会, 2016年08月, 日本腎臓学会誌, 58(6) (6), 917 - 917, 日本語Zebra body様蓄積物を水晶体上皮細胞に認めたE66Q変異の1症例会議報告等
- 日本糖尿病眼学会, 2016年03月, 日本糖尿病眼学会誌, 20, 103 - 103, 日本語光干渉断層計を用いた糖尿病網膜内層の2次元的評価
- (一社)日本糖尿病合併症学会, 2015年11月, 糖尿病合併症, 29(Suppl.1) (Suppl.1), 208 - 208, 日本語糖尿病黄斑浮腫に対するラニビズマブ硝子体注射の6ヵ月治療成績
- 眼科臨床紀要会, 2015年10月, 眼科臨床紀要, 8(10) (10), 762 - 763, 日本語ポリープ状脈絡膜血管症に対するアフリベルセプト併用光線力学的療法の6ヵ月成績
- 2015年06月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 56(7) (7), 英語The role of Mrp4 in pathological angiogenesis of the mouse retina研究発表ペーパー・要旨（国際会議）
- (株)じほう, 2015年06月, 調剤と情報, 21(7) (7), 864 - 868, 日本語【極める!副作用モニタリング】症例でわかる 実臨床で注意すべき副作用とモニタリング 眼科疾患記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）
- (公財)日本眼科学会, 2015年03月, 日本眼科学会雑誌, 119(臨増) (臨増), 178 - 178, 日本語病的網膜血管新生におけるMrp4の役割
- (公財)日本眼科学会, 2015年03月, 日本眼科学会雑誌, 119(臨増) (臨増), 196 - 196, 日本語続発性中心性漿液性脈絡網膜症における脈絡膜厚の検討
- (公財)日本眼科学会, 2015年03月, 日本眼科学会雑誌, 119(臨増) (臨増), 245 - 245, 日本語ポリープ状脈絡膜血管症に対するアフリベルセプト併用光線力学療法の12ヵ月成績
- 2014年, 日本網膜硝子体学会総会プログラム・講演抄録集, 53rdポリープ状脈絡膜血管症に対するアフリベルセプト併用光線力学的療法の6ケ月成績
- (公財)日本眼科学会, 2013年03月, 日本眼科学会雑誌, 117(臨増) (臨増), 312 - 312, 日本語フォルスコリンはMrp4KOマウスにおける網膜血管形成を修飾する
- (株)日本医事新報社, 2012年05月, 日本医事新報, (4593) (4593), 84 - 89, 日本語内科医のための眼科疾患の基礎知識記事・総説・解説・論説等（学術雑誌）
- 眼科臨床紀要会, 2011年10月, 眼科臨床紀要, 4(10) (10), 989 - 989, 日本語Macular hole indexの再現性の検討
- 眼科臨床紀要会, 2011年10月, 眼科臨床紀要, 4(10) (10), 994 - 994, 日本語ビスフォスフォネート薬内服による加齢黄斑変性予防効果の検討
- 眼科臨床紀要会, 2011年10月, 眼科臨床紀要, 4(10) (10), 1009 - 1009, 日本語受傷直後消失した視細胞内節外節接合部ラインが経時的に回復した鈍的眼外傷の1例
- 金原出版(株), 2011年06月, 眼科, 53(6) (6), 829 - 829, 日本語脈絡膜新生血管を合併したunilateral retinal pigment epithelium dysgenesisの一例
- (公財)日本眼科学会, 2011年04月, 日本眼科学会雑誌, 115(臨増) (臨増), 194 - 194, 日本語日本人加齢黄斑変性に対する遺伝情報を利用した光線力学療法の検討
- (公財)日本眼科学会, 2011年04月, 日本眼科学会雑誌, 115(臨増) (臨増), 206 - 206, 日本語Podoplanin制御による血管成熟のコントロールについて
- (公財)日本眼科学会, 2011年04月, 日本眼科学会雑誌, 115(臨増) (臨増), 226 - 226, 日本語内境界膜剥後のdissociated optic nerve fiber layerの頻度の検討
- (公財)日本眼科学会, 2011年04月, 日本眼科学会雑誌, 115(臨増) (臨増), 277 - 277, 日本語網膜内血管腫状増殖に対する光線力学単独療法とテノン嚢下トリアムシノロン併用の比較
- (公財)日本眼科学会, 2011年04月, 日本眼科学会雑誌, 115(臨増) (臨増), 277 - 277, 日本語近視性脈絡膜血管新生に対する光線力学療法と抗VEGF療法の治療成績
- 金原出版(株), 2011年01月, 眼科, 53(1) (1), 144 - 144, 日本語組織プラスミノーゲン活性化因子併用硝子体手術の有効性の評価
- (株)メディカ出版, 2010年12月, 眼科ケア, 12(12) (12), 1218 - 1224, 日本語【患者さんも納得・安心 レーザー治療はこわくない!】新人スタッフが押さえておきたい!レーザー治療の基礎知識
- 眼科臨床紀要会, 2010年10月, 眼科臨床紀要, 3(10) (10), 1010 - 1010, 日本語滲出型加齢黄斑変性と近視性脈絡膜血管新生に対するビスフォスフォネート内服治療
- 眼科臨床紀要会, 2009年11月, 眼科臨床紀要, 2(11) (11), 1069 - 1069, 日本語成人発症型卵黄状黄斑ジストロフィ3症例に関する遺伝子変異及び多型の検討
- 日本糖尿病眼学会, 2009年11月, 日本糖尿病眼学会誌, 14, 71 - 71, 日本語増殖糖尿病網膜症の経結膜硝子体手術における23、25ゲージ硝子体カッターの比較
- 眼科臨床紀要会, 2009年08月, 眼科臨床紀要, 2(8) (8), 763 - 763, 日本語Idiopathic juxtafoveolar retinal telangiectasis Type 3の1例
- 金原出版(株), 2009年06月, 眼科, 51(6) (6), 814 - 814, 日本語23G硝子体手術中の結膜嚢細菌の変化
- (株)文光堂, 2009年01月, 眼科プラクティス, 25, 320 - 321, 日本語【眼のバイオメトリー 眼を正確に測定する】黄斑裂孔のサイズ
- 金原出版(株), 2008年12月, 眼科, 50(13) (13), 1987 - 1987, 日本語ガス注入硝子体手術におけるアクリル眼内レンズの安定性について
- 眼科臨床紀要会, 2008年10月, 眼科臨床紀要, 1(10) (10), 1004 - 1004, 日本語23G硝子体手術後におけるSF6ガスの滞留期間と早期消失の関連因子
- 眼科臨床紀要会, 2008年10月, 眼科臨床紀要, 1(10) (10), 1010 - 1011, 日本語RAPに対するテノン嚢下トリアムシノロン併用PDTの長期成績
- (株)文光堂, 2008年09月, 眼科プラクティス, 23, 178 - 181, 日本語【眼科薬物治療A to Z】疾患別治療戦略と処方の実際 ぶどう膜疾患 APMPPE,PIC,MCP,AZOOR,MEWDS
- (株)文光堂, 2008年09月, 眼科プラクティス, 23, 206 - 207, 日本語【眼科薬物治療A to Z】One Point Advice 加齢黄斑変性におけるサプリメント使用について
- 日本糖尿病眼学会, 2008年09月, 日本糖尿病眼学会誌, 13, 98 - 98, 日本語隅角新生血管を伴う増殖糖尿病網膜症に対する23G硝子体手術
- 眼科臨床紀要会, 2008年05月, 眼科臨床紀要, 1(5) (5), 460 - 460, 日本語近視性脈絡膜新生血管に対する抗VEGF抗体(bevacizumab)硝子体内投与
- 眼科臨床紀要会, 2008年05月, 眼科臨床紀要, 1(5) (5), 462 - 462, 日本語血管新生緑内障と経結膜硝子体手術
- (株)文光堂, 2008年05月, 眼科プラクティス, 21, 381 - 381, 日本語【眼底画像所見を読み解く】One Point Advice 超音波画像診断
- 眼科臨床紀要会, 2008年04月, 眼科臨床紀要, 1(4) (4), 384 - 384, 日本語PDT後に発生した網膜色素上皮裂孔
- (株)医学書院, 2008年04月, 臨床眼科, 62(4) (4), 559 - 561, 日本語経結膜硝子体手術に併施する小切開白内障手術の切開径についての検討
- 眼科臨床医報会, 2007年09月, 眼科臨床医報, 101(9) (9), 925 - 925, 日本語ポリープ状脈絡膜血管症の病型による光線力学療法の治療効果の比較
- (株)文光堂, 2005年09月, 眼科プラクティス, 5, 336 - 337, 日本語【これならわかる神経眼科】神経眼科に関連の深い疾患 POEMS症候群
- 眼科臨床医報会, 2004年11月, 眼科臨床医報, 98(11) (11), 1012 - 1012, 日本語Dissociated Optic Nerve Fiber Layerは有害か?
- 眼科臨床医報会, 2004年11月, 眼科臨床医報, 98(11) (11), 1041 - 1041, 日本語嚢胞様黄斑浮腫を呈したCrow-Fukase症候群の1例
- 2004年04月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 45, U405 - U405, 英語Evaluation of successful macular hole surgery by multifocal electroretinography研究発表ペーパー・要旨（国際会議）
- (公財)日本眼科学会, 2004年03月, 日本眼科学会雑誌, 108(臨増) (臨増), 289 - 289, 日本語ヒヨコ後極網膜における光遮断の影響
- 日本神経眼科学会, 2003年12月, 神経眼科, 20(増補1) (増補1), 43 - 43, 日本語視神経疾患における乳頭周囲神経線維層厚と黄斑網膜厚の減少
- 日本神経眼科学会, 2003年12月, 神経眼科, 20(増補1) (増補1), 47 - 47, 日本語Band atrophyにおけるOCTによる網膜神経線維層厚の解析
- 日本神経眼科学会, 2003年12月, 神経眼科, 20(増補1) (増補1), 79 - 79, 日本語視索症候群の網膜神経線維層厚
- 2003年05月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 44, U548 - U548, 英語P53-mediated apoptosis in human RPE cells after low-dose radiation研究発表ペーパー・要旨（国際会議）
- 2003年05月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 44, U347 - U347, 英語A novel mutation in the RDH5 gene in a patient with macular dystrophy without white punctata研究発表ペーパー・要旨（国際会議）
- 2003年05月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 44, U395 - U395, 英語Platelet-derived growth Factor-BB generate neural stem cells from proliferating retinal astrocytes研究発表ペーパー・要旨（国際会議）
- 2003年05月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 44, U395 - U395, 英語Light deprivation induces the increase of undifferentiated cells in the posterior pole of post-hatch chick eyes研究発表ペーパー・要旨（国際会議）
- 2003年05月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 44, U103 - U103, 英語Evaluation of macular thickness using retinal mapping of optical coherence tomography after macular hole surgery研究発表ペーパー・要旨（国際会議）
- 2003年05月, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 44, U100 - U100, 英語Evaluation of retinal nerve fiber layer thickness by optical coherence tomography in eyes with idiopathic macular holes after vitrectomy with internal limiting membrane peeling研究発表ペーパー・要旨（国際会議）
- (公財)日本眼科学会, 2003年03月, 日本眼科学会雑誌, 107(臨増) (臨増), 176 - 176, 日本語特発性黄斑円孔に対する硝子体手術後の視力と術前fluid cuffの関係
- (公財)日本眼科学会, 2003年03月, 日本眼科学会雑誌, 107(臨増) (臨増), 336 - 336, 日本語マウス網膜におけるPlatelet-Derived Growth Factor刺激によるアストロサイト由来神経幹細胞の発現について
- (公財)日本眼科学会, 2003年03月, 日本眼科学会雑誌, 107(臨増) (臨増), 341 - 341, 日本語内境界膜剥離を併用した黄斑円孔術後の網膜神経線維層厚(RNFLT)の変化
- 日本神経眼科学会, 2002年10月, 神経眼科, 19(増補1) (増補1), 42 - 42, 日本語鈍的眼外傷後発症した非定型的レーベル病の1例
- 日本神経眼科学会, 2002年10月, 神経眼科, 19(増補1) (増補1), 47 - 47, 日本語前部虚血性視神経症の網膜神経線維層の推移
- (株)メディカル葵出版, 2002年10月, あたらしい眼科, 19(10) (10), 1279 - 1283, 日本語【小児神経眼科】小児視神経疾患
- 眼科臨床医報会, 2002年09月, 眼科臨床医報, 96(9) (9), 995 - 995, 日本語神戸大学眼科における眼球運動障害症例の統計的検討
- (株)文光堂, 2002年07月, 眼科診療プラクティス, 84, 69 - 69, 日本語【眼の光障害】検者,術者の光障害
- (株)医学書院, 2002年03月, 臨床眼科, 56(3) (3), 283 - 287, 日本語眼窩先端部症候群として発症した眼窩真菌感染症の1例
- 眼科臨床医報会, 2002年01月, 眼科臨床医報, 96(1) (1), 83 - 83, 日本語加齢黄斑変性に自然発生した大量脈絡膜出血の2例
- 2001年10月09日, 抄録集, 18, 111 - 111, 日本語神戸大学眼科における眼球運動障害症例の統計的検討
- 眼科臨床医報会, 2001年05月, 眼科臨床医報, 95(5) (5), 558 - 558, 日本語Pneumatic displacementを施行した3症例
- 眼科臨床医報会, 2001年05月, 眼科臨床医報, 95(5) (5), 557 - 557, 日本語梅毒性視神経症の3例
- 眼科臨床医報会, 2001年05月, 眼科臨床医報, 95(5) (5), 558 - 558, 日本語網膜血管腫に対する治療の検討
- (公財)日本眼科学会, 2001年03月, 日本眼科学会雑誌, 105(臨増) (臨増), 349 - 349, 日本語外傷性視神経障害における視野障害の再検討
- 眼科臨床医報会, 2001年02月, 眼科臨床医報, 95(2) (2), 193 - 193, 日本語眼外傷後に顕性化した上斜筋麻痺の1例
- 眼科臨床医報会, 2000年11月, 眼科臨床医報, 94(11) (11), 1382 - 1382, 日本語当科での外傷性視神経障害治療の変遷
- 日本神経眼科学会, 2000年11月, 神経眼科, 17(増補) (増補), 102 - 102, 日本語当科での外傷性視神経障害治療の変遷と成績
- 眼科臨床医報会, 2000年02月, 眼科臨床医報, 94(2) (2), 220 - 220, 日本語当科で経験したADEM症例の検討
- 日本神経眼科学会, 1999年09月, 神経眼科, 16(増補) (増補), 57 - 57, 日本語眼虚血症候群での眼動脈カラードップラー検査
- 眼科臨床医報会, 1999年07月, 眼科臨床医報, 93(7) (7), 1117 - 1117, 日本語糖尿病を伴う眼虚血症候群の虹彩ルベオーシス
- その他, 中山書店, 2018年02月, 日本語眼科診療ビジュアルラーニング２ 眼炎症 / 術後にみられた炎症/遅発性術後眼内炎学術書
- その他, 日本医事新報社, 2012年05月, 日本語日本医事新報 / 内科医のための眼科疾患の基礎知識学術書
- 共著, メディカ出版, 2010年12月, 日本語眼科ケア / 新人スタッフが押さえておきたい！ レーザー治療の基礎知識学術書
- 共著, メディカ出版, 2010年12月, 日本語眼科ケア / 患者さんも納得・安心 レーザー治療はこわくない！学術書
- 共著, 文光堂, 2010年, 日本語眼のサイエンス 眼疾患の謎 / 高度の嚢胞様黄斑浮腫があっても視力良好な症例があるのはなぜか？学術書
- 共著, 文光堂, 2009年01月, 日本語眼科プラクティス25巻 【眼のバイオメトリー 眼を正確に測定する】 / 黄斑裂孔のサイズ学術書
- 共著, 文光堂, 2008年09月, 日本語眼科プラクティス 【眼科薬物治療A to Z】 / One Point Advice 加齢黄斑変性におけるサプリメント使用について(解説/特集)教科書・概説・概論
- 共著, 文光堂, 2008年09月, 日本語眼科プラクティス23巻 【眼科薬物治療A to Z】 / 疾患別治療戦略と処方の実際 ぶどう膜疾患 APMPPE,PIC,MCP,AZOOR,MEWDS(解説/特集)教科書・概説・概論
- 共著, 文光堂, 2008年05月, 日本語眼科プラクティス21巻 【眼底画像所見を読み解く】 / One Point Advice 超音波画像診断(解説/特集)教科書・概説・概論
- 共著, 文光堂, 2005年09月, 日本語眼科プラクティス 【これならわかる神経眼科】 / 神経眼科に関連の深い疾患 POEMS症候群学術書
- 第57回日本網膜硝子体学会総会, 2018年12月, 日本語, 京都, 国内会議滲出型加齢黄斑変性の固視に関する検討口頭発表（一般）
- 第57回日本網膜硝子体学会総会, 2018年12月, 日本語, 京都, 国内会議En face slab OCT像を用いた網膜静脈分枝閉塞症の乳頭黄斑線維束障害についての検討口頭発表（一般）
- 第5回神戸大学眼科オープンカンファレンス, 2018年11月, 日本語, 神戸, 国内会議下垂体茎断裂症候群に対するホルモン治療中に進行性の網膜変性症の合併を認めた１症例口頭発表（一般）
- 第5回神戸大学眼科オープンカンファレンス, 2018年11月, 日本語, 神戸, 国内会議サイトメガロウイルス虹彩炎に起因する続発性緑内障 15 例の臨床像口頭発表（一般）
- 第72回日本臨床眼科学会, 2018年10月, 日本語, 東京, 国内会議糖尿病眼におけるslab en face OCT像と網膜内層厚口頭発表（一般）
- 第33回日糖尿病合併症学会・第24回日本糖尿病眼学会総会, 2018年10月, 日本語, 東京, 国内会議糖尿病黄斑浮腫治療成績とOCT en face slab像の関係口頭発表（一般）
- 第72回日本臨床眼科学会, 2018年10月, 日本語, 東京, 国内会議ぶどう膜炎続発緑内障に対するテノン開創器を用いた線維柱帯切除術の短期成績口頭発表（一般）
- 第72回日本臨床眼科学会, 2018年10月, 日本語, 東京, 国内会議Vogt-小柳-原田病治療後の脈絡膜構造変化と再発前変動の検討口頭発表（一般）
- 日本臨床視覚電気生理学会, 2018年09月, 日本語, 浜松, 国内会議下垂体茎断裂症候群に対するホルモン治療中に進行性の網膜変性症の合併を認めた１例口頭発表（一般）
- 第22回眼創傷治癒研究会, 2018年07月, 日本語, 奈良, 国内会議続発緑内障に対するテノン開創器を用いた線維柱帯切除術口頭発表（一般）
- 第52回日本眼炎症学会, 2018年07月, 日本語, 東京, 国内会議神戸大学眼科における非感染性ぶどう膜炎に対するアダリムマブの使用経験口頭発表（一般）
- フォーサム2018東京, 2018年07月, 英語, 東京, 国内会議International Distinguished Papers Symposium Characteristics of vitreous cells in uveitis on optical coherence tomography口頭発表（一般）
- 第122回日本眼科学会総会, 2018年04月, 日本語, 大阪, 国内会議続発緑内障に対するテノン開創器を用いた線維柱帯切除術の短期成績口頭発表（一般）
- 第122回日本眼科学会総会, 2018年04月, 日本語, 大阪, 国内会議光干渉断層計slab en face像を用いた糖尿病網膜内層構造変化の評価口頭発表（一般）
- 第122回日本眼科学会総会, 2018年04月, 日本語, 大阪, 国内会議ポリープ状脈絡膜血管症へのアフリベルセプト併用光線力学療法後の網膜色素上皮萎縮口頭発表（一般）
- 第122回日本眼科学会総会, 2018年04月, 日本語, 大阪, 国内会議アクアポリン9 遺伝子欠損マウスにおける視神経挫滅後の網膜神経節細胞死口頭発表（一般）
- ARVO, 2018年04月, 英語, ホノルル, 国際会議Structural changes in the inner retina assessed by slab en face optical coherence tomography in diabetic eyes.口頭発表（一般）
- ARVO, 2018年04月, 英語, ホノルル, 国際会議Evaluation of vitreoretinal cellular infiltration in uveitis on optical coherence tomography.口頭発表（一般）
- 第46回 日本腎臓学会西部学術大会, 2016年10月, 日本語, 日本腎臓学会, Ｍｉｙａｚａｋｉ, 宮崎, 国内会議Zebra-body蓄積物水晶体上皮細胞に認めたE66Q変異の1症例口頭発表（一般）
- フォーサム2013大阪, 2013年07月, 日本語, 日本眼炎症学会, 大阪, 国内会議片眼のYAG後嚢切開術後に両眼の前房蓄膿を呈した若年性慢性虹彩毛様体炎の1例口頭発表（一般）
- 第117回日本眼科学会総会, 2013年04月, 日本語, 日本眼科学会, 東京, 国内会議フォルスコリンはMrp4KO マウスにおける網膜血管形成を修飾する口頭発表（一般）
- 第66回日本臨床眼科学会, 2012年10月, 日本語, 日本眼科学会, 京都, 国内会議中心性漿液性脈絡網膜症に対する光線力学療法のレーザー照射径と治療効果に関する検討口頭発表（一般）
- 第46回日本眼炎症学会, 2012年07月, 日本語, 日本眼炎症学会, 横浜, 国内会議結核性ぶどう膜炎に組織プラスミノーゲン活性化因子硝子体注射を施行した2例口頭発表（一般）
- 第46回日本眼炎症学会, 2012年07月, 日本語, 日本眼炎症学会, 横浜, 国内会議クリオグロブリン血症に伴う血管炎から網膜静脈分枝閉塞症を発症した1症例口頭発表（一般）
- 第116回日本眼科学会総会, 2012年04月, 日本語, 日本眼科学会, 東京, 国内会議中心性漿液性脈絡網膜症におけるARMS2およびCFH多型の検討口頭発表（一般）
- 第116回日本眼科学会総会, 2012年04月, 日本語, 日本眼科学会, 東京, 国内会議近視性脈絡膜血管新生に対するビスフォスフォネート薬内服の中期効果口頭発表（一般）
- 第116回日本眼科学会総会, 2012年04月, 日本語, 日本眼科学会, 東京, 国内会議ranibizumab硝子体内投与後のAMD再発例における臨床的及び遺伝的関連因子の検討口頭発表（一般）
- 第430回日本皮膚科学会大阪地方会, 2012年03月, 日本語, 大阪地方会, 大阪, 国内会議弾性線維性仮性黄色腫の2例口頭発表（一般）
- 第65回日本臨床眼科学会, 2011年10月, 日本語, 日本大学, 東京, 国内会議狭義加齢黄斑変性とポリープ状脈絡膜血管症に対するranibizumab 硝子体注射の治療成績口頭発表（一般）
- 第65回日本臨床眼科学会, 2011年10月, 日本語, 日本大学, 東京, 国内会議狭義加齢黄斑変性とポリープ状脈絡膜血管症におけるCD36遺伝子多型口頭発表（一般）
- スリーサム2011, 2011年07月, 日本語, 日本眼感染症学会・日本眼炎症学会・日本ｺﾝﾀｸﾄﾚﾝｽﾞ学会, 京都, 国内会議非肉芽腫性ぶどう膜炎を伴ったSweet症候群の2症例口頭発表（一般）
- 第115回日本眼科学会総会, 2011年05月, 日本語, 日本眼科学会, 東京, 国内会議網膜内血管腫状増殖に対する光線力学単独療法とテノン嚢下トリアムシノロン併用の比較口頭発表（一般）
- 第115回日本眼科学会総会, 2011年05月, 日本語, 日本眼科学会, 東京, 国内会議日本人加齢黄斑変性に対する遺伝情報を利用した光線力学療法の検討口頭発表（一般）
- 第115回日本眼科学会総会, 2011年05月, 日本語, 日本眼科学会, 東京, 国内会議内境界膜剥離後のdissociated optic nerve fiber layerの頻度の検討口頭発表（一般）
- 第115回日本眼科学会総会, 2011年05月, 日本語, 日本眼科学会, 東京, 国内会議近視性脈絡膜血管新生に対する光線力学療法と抗VEGF療法の治療成績口頭発表（一般）
- 視覚と眼科学研究協会会議, 2011年05月, 英語, Association for Research in Vision and Ophthalmology, フォートローダデール, 米国, 国際会議The Early Responses To Intravitreal Ranibizumab In Typical Neovascular Age-related Macular Degeneration And Polypoidal Choroidal Vasculopathy.口頭発表（一般）
- 第115回日本眼科学会総会, 2011年05月, 日本語, 日本眼科学会, 東京, 国内会議Podoplanin制御による血管成熟のコントロールについて口頭発表（一般）
- 第33回日本造血細胞移植学会総会, 2011年03月, 日本語, 日本造血細胞移植学会, 松山, 国内会議臍帯血移植前にﾎﾞﾘｺﾅｿﾞｰﾙ水晶体内投与が有効であった真菌性眼内炎ポスター発表
- 第49回日本網膜硝子体学会総会, 2010年11月, 日本語, 日本網膜硝子体学会, 大阪, 国内会議脈絡膜新生血管を合併したUnilateral retinal pigment epithelium dysgenesisの1例口頭発表（一般）
- 第49回日本網膜硝子体学会総会, 2010年11月, 日本語, 日本網膜硝子体学会, 大阪, 国内会議受傷直後消失した視細胞内節外節接合部ラインが軽時的に回復した鈍的眼外傷の1例口頭発表（一般）
- 第49回日本網膜硝子体学会総会, 2010年11月, 日本語, 日本網膜硝子体学会, 大阪, 国内会議ビスフォスフォネート薬内服による加齢黄斑変性予防効果の検討口頭発表（一般）
- 第49回日本網膜硝子体学会総会, 2010年11月, 日本語, 日本網膜硝子体学会, 大阪, 国内会議Macular hole indexの信頼性の検討口頭発表（一般）
- 第27回日本眼循環学会, 2010年07月, 日本語, 日本眼循環学会, 神戸, 国内会議網膜静脈閉鎖症に対する組織ﾌﾟﾗｽﾐﾉｰｹﾞﾝ活性化因子硝子体内投与前後での網膜電図口頭発表（一般）
- 第47回日本眼感染症学会, 2010年07月, 日本語, 日本眼感染症学会, 東京, 国内会議自己免疫性網膜症における臨床像の検討口頭発表（一般）
- 第44回日本眼炎症学会, 2010年07月, 日本語, 日本眼炎症学会, 東京, 国内会議自己免疫性網膜症における臨床像の検討口頭発表（一般）
- 第47回日本眼感染症学会, 2010年07月, 日本語, 日本眼感染症学会, 東京, 国内会議リンパ腫様肉芽腫症にサイトメガウイルス網膜炎を伴った1例口頭発表（一般）
- WOC2010, 2010年06月, 英語, International Council of Ophthalmology, ベルリン, ドイツ, 国際会議Therapeutic effect of oral bisphosphonate on choroidal neovascularization in the human eye口頭発表（一般）
- WOC2010, 2010年06月, 英語, International Council of Ophthalmology, ベルリン, ドイツ, 国際会議Surgical and visual outcome after autologous plasmin assisted vitrectomy for stage5 retinopathy of prematurity口頭発表（一般）
- ARVO2010, 2010年05月, 英語, Association for Research in Vision and Ophthalmology, ﾌｫｰﾄﾛ-ﾀﾞｰﾃﾞｰﾙ, 米国, 国際会議Knock down of Multidrug Resistance Associaeted Protein 4 by Sirna Enhances enhances Cell Migtation and Tube Formation in human retinal vascular endothelial cells.口頭発表（一般）
- ARVO2010, 2010年05月, 英語, Association for Research in Vision and Ophthalmology, ﾌｫｰﾄﾛ-ﾀﾞｰﾃﾞｰﾙ, 米国, 国際会議A Novel Profiling System of Evdothelial Gene Expression in Angiogenic Retinal Vessels.口頭発表（一般）
- 第114回日本眼科学会総会, 2010年04月, 日本語, 日本眼科学会, 名古屋, 国内会議中心性漿液性脈絡網膜症眼の白内障術後に視神経乳頭に連続した網膜分離症が生じた1例口頭発表（一般）
- 第114回日本眼科学会総会, 2010年04月, 日本語, 日本眼科学会, 名古屋, 国内会議ポリープ状脈絡膜血管症に対する光線力学的療法における抗凝固薬内服の影響口頭発表（一般）
- 第45回日本網膜硝子体学会総会, 2006年12月, 日本語, 日本網膜硝子体学会, 東京, 国内会議ポリープ状脈絡膜血管症の病型による光線力学療法の治療効果の比較口頭発表（一般）
- 第7回上方黄斑研究会, 2006年08月, 日本語, 上方黄斑研究会, 大阪, 国内会議浮腫？分離？口頭発表（一般）
- SummerEyeSummit, 2006年07月, 日本語, 神戸, 国内会議長期経過を経てポリープ状脈絡膜血管症を発症した中心性漿液性脈絡網膜症の1例口頭発表（一般）
- 第４４回日本網膜硝子体学会総会, 2005年12月, 日本語, 大阪, 国内会議Dissociated Optic Nerve Fiber Layer 眼における視機能、網膜神経線維層厚の評価口頭発表（一般）
- 第４２回日本神経眼科学会総会, 2004年10月, 日本語, 日本神経眼科学会, 名古屋, 国内会議相対的求心性瞳孔障害と光干渉断層計で測定した網膜神経線維層の関係口頭発表（一般）
- International Neuro-Ophthalmology Socuety XV.Meeting, 2004年07月, 英語, International Neuro-Ophthalmology, ジュネーブ, 国際会議Optic nerve sheath meningioma rapidly manifesting various ocular complications.ポスター発表
- International Neuro-Ophthalmology Socuety XV.Meeting, 2004年07月, 英語, International Neuro-Ophthalmology, ジュネーブ, 国際会議Macular thickness changes in optic atrophy detedted with optical coherence tomography.ポスター発表
- International Neuro-Ophthalmology Socuety XV.Meeting, 2004年07月, 英語, International Neuro-Ophthalmology, ジュネーブ, 国際会議Heidelderg Retina Tomograph can objectively assess differential optic nerve head configuration in various types of optic neuropagthy.ポスター発表
- 第２９回日本小児眼科学会、第60回日本弱視斜視学会, 2004年06月, 日本語, 日本小児眼科学会、日本弱視斜視学会, 沖縄, 国内会議小児白内障術後の近見、遠見視力発達口頭発表（一般）
- 第１１０回京都眼科学会, 2004年06月, 日本語, 京都眼科学会, 京都, 国内会議黄斑浮腫に対するトリアムシノロン後部テノン嚢下注射の治療成績口頭発表（一般）
- 第１０８回日本眼科学会総会, 2004年04月, 日本語, 日本眼科学会, 東京, 国内会議ヒヨコ後極網膜における光遮断の影響口頭発表（一般）
- 第１０回日本糖尿病眼学会, 2004年03月, 日本語, 日本糖尿病眼学会, 福岡, 国内会議黄斑浮腫に対するｹﾅｺﾙﾄ後部ﾃﾉﾝ嚢下注射の治療成績口頭発表（一般）
- 第２７回日本眼科手術学会総会, 2004年01月, 日本語, 日本眼科手術学会, 東京, 国内会議ｲﾝﾄﾞｼｱﾆﾝｸﾞﾘｰﾝ染色を用いた内境界膜剥離後の網膜神経線維層厚の変化口頭発表（一般）
- 第２７回日本眼科手術学会総会, 2004年01月, 日本語, 日本眼科手術学会, 東京, 国内会議特発性黄斑円孔のおける術後glisteningと視力の関係口頭発表（一般）
- 第４２回日本網膜硝子体学会総会、第20回眼病理ｾﾐﾅｰ, 2003年12月, 日本語, 日本網膜硝子体学会, 福岡, 国内会議白点が自然消退した黄斑変性を伴う眼底白点症の一例口頭発表（一般）
- 第４２回日本網膜硝子体学会総会、第20回眼病理ｾﾐﾅｰ, 2003年12月, 日本語, 日本網膜硝子体学会, 福岡, 国内会議嚢胞様黄斑浮腫を呈したCrow-Fukase症候群の一例口頭発表（一般）
- 第４２回日本網膜硝子体学会総会、第20回眼病理ｾﾐﾅｰ, 2003年12月, 日本語, 日本網膜硝子体学会, 福岡, 国内会議内境界膜剥離を併用した黄斑円孔術後の網膜神経線維層厚の変化口頭発表（一般）
- 第４１回日本神経眼科学会, 2003年12月, 日本語, 日本神経眼科学会, 京都, 国内会議視神経疾患における乳頭周囲神経線維層厚と黄斑網膜厚の減少口頭発表（一般）
- 第４１回日本神経眼科学会, 2003年12月, 日本語, 日本神経眼科学会, 京都, 国内会議視索症候群の網膜神経線維層厚口頭発表（一般）
- 第４２回日本網膜硝子体学会総会、第20回眼病理ｾﾐﾅｰ, 2003年12月, 日本語, 日本網膜硝子体学会, 福岡, 国内会議Dissociated Optic Nerve Fiber Layerは有害か？口頭発表（一般）
- 第４１回日本神経眼科学会, 2003年12月, 日本語, 日本神経眼科学会, 京都, 国内会議Band atrophyにおけるOCTによる網膜神経線維層厚の解析口頭発表（一般）
- 第１０３回兵庫県眼科医会学術集談会, 2003年10月, 日本語, 日本眼科医会, 神戸大学, 国内会議６０年の歳月を経て観察できた眼底白点症の一例口頭発表（一般）
- 第６９回日本中部眼科学会、第１００回中国四国眼科学会, 2003年10月, 日本語, 日本中部眼科学会、, 岡山, 国内会議僚眼の発症により確定診断したポリープ状脈絡膜血管症の１例口頭発表（一般）
- 第１０３回兵庫県眼科医会学術集談会, 2003年10月, 日本語, 日本眼科医会, 神戸大学, 国内会議僚眼の発症によりポリープ状脈絡膜血管症と診断した一例口頭発表（一般）
- 第５７回日本臨床眼科学会, 2003年10月, 日本語, 日本臨床眼科学会, 名古屋, 国内会議ポリープ状脈絡膜血管症より急激に発生した脈絡膜血管腫の一例口頭発表（一般）
- 第５７回日本臨床眼科学会, 2003年10月, 日本語, 日本臨床眼科学会, 名古屋, 国内会議インドシアニングリーン染色を用いた内境界膜剥離施行後の多局所網膜電位図口頭発表（一般）
- 第６９回日本中部眼科学会、第１００回中国四国眼科学会, 2003年10月, 日本語, 日本中部眼科学会、中国四国眼科学会, 岡山, 国内会議M-CHARTSによる黄斑上膜と中心漿液性脈絡網膜症の変視量の検討口頭発表（一般）
- 第１０９回京都眼科学会, 2003年06月, 日本語, 京都眼科学会, 京都, 国内会議白点が自然消退した眼底白点症の一例口頭発表（一般）
- 第１０９回京都眼科学会, 2003年06月, 日本語, 京都眼科学会, 京都, 国内会議黄斑疾患における定量的形態評価口頭発表（一般）
- 第１０３回兵庫県眼科医会学術集談会, 2003年05月, 日本語, 兵庫県眼科医会, 兵庫医大, 国内会議黄斑疾患におけるMチャート口頭発表（一般）
- ARVO 2003, 2003年05月, 英語, ARVO, Lauderdale, 国際会議Light deprivation induces the increase of indifferentiated cells in the posterior pole of post-hatch chick eyes.ポスター発表
- ARVO 2003, 2003年05月, 英語, ARVO, Lauderdale, 国際会議Evaluation of retinal nerve fiber layer thickness by optical coherence tomography in eyes with idiopathic macular holes after vitrectomy with internal limiting membrance peeling.ポスター発表
- ARVO 2003, 2003年05月, 英語, ARVO, Lauderdale, 国際会議Evaluation of macular thickness using retina mapping of optical coherence tomography after macular hole surgery.ポスター発表
- ARVO 2003, 2003年05月, 英語, ARVO, Lauderdale, 国際会議A novel mutation in the RDH5 gene in a patient with macular dystrophy without white punctata.ポスター発表
- Association for Research in Vision and Ophthalmology, 2003年05月, 英語, Association for Research in Vision and Ophthalmology, Ft. Lauderdale, 国際会議A novel mutation in the RDH5 gene in a patient with macular dystrophy without white punctataポスター発表
- 第１０７回日本眼科学会総会, 2003年04月, 日本語, 日本眼科学会, 福岡, 国内会議内境界膜剥離を併用した黄斑円孔術後の網膜神経線維層厚(RNFLT)の変化口頭発表（一般）
- 第１０７回日本眼科学会総会, 2003年04月, 日本語, 日本眼科学会, 福岡, 国内会議特発性黄斑円孔に対する焼死体手術後の視力と術前fluid cuffの関係口頭発表（一般）
- 第２２回神戸市立中央市民病院眼科ｵｰﾌﾟﾝカンファレンス, 2003年03月, 日本語, 神戸市立中央市民病院, 神戸, 国内会議当院における滲出性加齢黄斑変性症の長期経過口頭発表（一般）
- 第２２回神戸市立中央市民病院眼科ｵｰﾌﾟﾝカンファレンス, 2003年03月, 日本語, 神戸市立中央市民病院, 神戸, 国内会議異常な形態を示したvitreomacular traction syndromeの１例口頭発表（一般）
- 第２６回日本眼科手術学会, 2003年01月, 日本語, 日本眼科手術学会, 京都, 国内会議特発性黄斑円孔における硝子体牽引の指標としてのfluid cuff形態口頭発表（一般）
- 日本学術振興会, 科学研究費助成事業, 基盤研究(B), 神戸大学, 2024年04月01日 - 2027年03月31日乳酸シャトル・情報伝達障害としての緑内障性視神経症の病態論の提唱と治療法の探索
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2021年04月01日 - 2024年03月31日乳酸シャトル概念に基づく網膜・視神経変性疾患の病態解明と治療法の探索マウス高眼圧モデルとして、マイクロビーズと粘弾性物質の前房内注入によって4週にわたり眼圧上昇できることを確認した。このマウスで、網膜進展標本を作製し、TUJ1免疫染色くを行ったところ、網膜神経節細胞が経時的に有意に脱落することをで確認した。Weestern blotting, 免疫沈降、ならびに免疫染色により、高眼圧モデルマウスでは、網膜内アクアポリン9(AQP9)、monocarboxylate transporter (MCT)1,2,4の発現が有意に低下していた。 視神経挫滅モデル１週で、24時間案順応後に暗所視閾値電位(STR)を測定したところ、STRが有意に低下した一方で、強い刺激によるa波、b波には変化はなく、このSTRの変化は視細胞や双極細胞の変化に続発するものではなく、網膜神経節細胞の機能低下であることが示された。また網膜伸展標本とTUJ1免疫染色で、高眼圧モデル同様網膜神経節細胞死が有意に増加した。また同じく、AQP9, MCT1,2,4の発現低下がみられた。 視神経挫滅マウスに高濃度乳酸を吸入麻酔下で3時間腹腔内投与することにより、網膜神経節細胞死、STR低下、AQP9, MCT1,2,4の発現低下は有意に改善した。 網膜の解糖系、電子伝達系の基質を質量分析装置でメタボローム解析を行ったところ、網膜内ではglucoseよりもL-lactateの濃度の方が有意に高かった。 網膜では定常状態下でも乳酸がグルコースよりも豊富に存在し、高眼圧や視神経挫滅で乳酸輸送体の発現が低下し、網膜神経節細胞の機能不全と細胞死が生じるが、外因性の乳酸投与が神経保護効果を発揮する可能性が示された。
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2021年04月01日 - 2024年03月31日糖尿病網膜神経変性におけるアクアポリン９の役割の解明1.研究内容:遺伝子改変糖尿病マウスを安定的に得るためにInsCre;Pdkflox/+マウスとPdkflox/floxマウスを用いた体外受精を行い凍結受精卵を作成した。このことによって、任意の時期にInsCre;Pdkflox/flox（糖尿病マウス）およびPdkflox/floxマウス（コントロールマウス）を得ることができるようになった。遺伝子改変マウスCx3cr1-GFPマウス（ミクログリア標識）およびアデノ随伴ウイルス（アストロサイト、網膜神経節細胞）による標識を適宜利用し、糖尿病マウスでの２光子顕微鏡による生体イメージングを行った。ミクログリアの動きおよび形態変化を定量化する方法につき複数のアルゴリズムをトライし、安定して評価できる系が確立されつつある。また、AQP9の糖尿病網膜神経変性における役割の解明を進めるために、InsCre;Pdkflox/flox;Aqp9-/-マウスおよびPdkflox/flox;Aqp9+/-マウス（コントロール）の安定供給に向けマウスの交配を続けていると同時にAqp9-/-マウスにストレプトゾトシンを投与し高血糖を誘発して解析を進めている。 2.研究の意義:多面的な神経保護作用を有する乳酸のトランスポーターであるAQP9は糖尿病早期における糖尿病網膜神経変性に関与している可能性が高い。慢性炎症の際に早期から異常が認められるミクログリアの変化が２光子顕微鏡による生体イメージングで解析できていることから、この研究を続けることによって糖尿病網膜におけるAQP9の役割が明らかになるものと思われる。 3. 研究の重要性:本研究によって糖尿病早期におけるAQP9の役割が明らかになれば、乳酸をターゲットにした糖尿病網膜症への早期介入への道筋が示されることになり将来の失明予防に大いに貢献できると考える。
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2018年04月01日 - 2021年03月31日, 研究代表者糖尿病網膜におけるneurovascular unit障害とアストロサイトを標識し２光子顕微鏡を用いたin vivoイメージングを行った。 1. 研究内容:糖尿病マウス網膜におけるneurovascular unit障害の進行を明らかにするためにneurovascular unit構成細胞である、血管内皮細胞、周皮細胞、アストロサイト、網膜神経節細胞、ミクログリア、細胞外マトリックスの変化を免疫染色で経時的（生後4週、12週、20週）に評価しコントロールマウスと糖尿病マウス(InsCre;Pdk1flox/floxマウス)での比較を行ったところ、生後12週から細胞外マトリクスと網膜神経節細胞の変化が出現するがその他の細胞については明らかな形態変化が認められなかった（ミクログリアについては染色が上手くワークしなかったことからCx3cr1-GFPマウスを用いた解析を予定している）。網膜アストロサイトのin vivoイメージングについてはアデノ随伴ウイルスの硝子体注射によってアストロサイトを標識し撮影することに成功しているが予想に反して動きが少なく活動性の評価が難しいと思われた。また網膜像の解像度を向上させるために撮影用コンタクトレンズをさらに改良した。 2. 研究の意義: 実験結果から持続高血糖下では明らかなアストロサイト形態異常が生じる前に網膜神経節細胞障害が生じていることが確認できた。この段階におけるアストロサイトの機能的変化を可視化できれば高血糖におけるneurovascular unit障害を早期に評価できると考える。 3. 研究の重要性:本研究によって糖尿病早期における細胞レベルでの網膜機能評価を可能にするする技術が確立されれば糖尿病網膜症による失明予防に大いに貢献できると考える。競争的資金
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2018年04月01日 - 2021年03月31日2010～2017年に血液浄化療法を行った抗アクアポリン4抗体陽性視神経炎患者連続9例15眼の視機能予後を後ろ向きに検討した。いずれもステロイドパルス療法に抵抗性であった。12眼(80%)においてlogMAR換算で0.3以上の視力改善を見た。その大半が1年後にも良好な視力を保ち、早期の血液浄化療法が視神経脊髄炎患者の視機能回復に有効であることを報告した(Mori S, Nakamura M, et al.Jpn J Ophthalmol. 2018;62(4):525-530)。 AQP9 knowkout (KO) マウスにおいて、視神経挫滅後の網膜神経節細胞死が野生型マウスに比べて、有意に多かった。また、免疫沈降とWestern blottingにより、野生型マウスにおいては、網膜や視神経にmonocarboxylate transporter (MCT)4がAQP9と共発現していること、一方、AQP9 KOマウスや視神経挫滅後にはMCT4の発現が代償性に増加することを見出した。網膜においてエネルギー基質である乳酸の輸送を司る二つのtransporter（AQP9とMCT4）が、網膜神経節細胞において共発現していること、ならびにどちらかの一方のみ発現している場合、naiveな網膜神経節細胞の生存は維持できるが、視神経挫滅のようなストレス下では、代償機転は働くものの、生存を維持できない可能性が示唆された。競争的資金
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2015年04月01日 - 2018年03月31日, 研究代表者Multidrug resistance protein 4 (Mrp4)ノックアウトマウスでは野生型マウスに比較してストレプトゾトシン誘発高血糖における有意な網膜血管密度の低下が認められた。InsCreTg; Pdk1flox/floxマウスでは明らかな網膜血管の異常がない段階で、ラミニンの菲薄化と網膜神経線維の減少が生じていることが判明した。糖尿病初期の網膜細胞異常を評価するために２光子顕微鏡を用いた網膜生体イメージングの系をマウスで確立した。これらの成果は糖尿病網膜症の病態解明に役立つと考えられる。競争的資金
- 日本学術振興会, 科学研究費助成事業 若手研究(B), 若手研究(B), 神戸大学, 2012年04月01日 - 2015年03月31日, 研究代表者本研究では、排出型トランスポーターであるMrp4が細胞内cAMP濃度の調節を介して生理的網膜血管新生に複雑に関与していることが示された。また、酸素誘発網膜症において無血管領域の形成と網膜外血管新生がMrp4ノックアウトマウスで増悪したことから、Mrp4が病的網膜血管新生に対して抑制的に働いていると考えられた。これらの結果から、Mrp4が網膜血管増殖疾患の治療ターゲットとなる可能性を見出した。競争的資金
- 日本学術振興会, 科学研究費助成事業 若手研究(B), 若手研究(B), 神戸大学, 2010年 - 2011年, 研究代表者Multidrug resistance protein 4(MRP4)はABCトランスポーターファミリーに属する膜蛋白である。ヒト網膜毛細血管内皮細胞を用いた細胞培養実験では、MRP4ノックダウンによって細胞遊走増加、アポトーシス抑制、異常凝集形態、が認められた。ノックアウトマウスを用いた実験ではMrp4の基質であるcAMPの細胞内濃度を上昇させる薬剤であるフォルスコリンの腹腔内注射によって網膜毛細血管の異常増生が認められた。これらの結果からMRP4が網膜血管新生に対して抑制的に働いていると推測される。競争的資金
研究シーズ
■ 研究シーズ- 糖尿病網膜神経変性におけるアクアポリン９の役割の解明シーズカテゴリ：ライフサイエンス研究キーワード：糖尿病網膜症, 神経変性, アクアポリン９, 生体イメージング研究の背景と目的： 私たちは糖尿病の発症早期から糖尿病網膜神経変性に対する治療介入を行うことによって周皮細胞脱落に続く血液網膜柵の破綻を抑制するというシナリオを描いており、治療のターゲットとして中枢神経で神経保護的に働くアクアポリン９(AQP9)に注目しました。本研究では遺伝子改変マウスと２光子顕微鏡を用いた生体イメージングで糖尿病網膜神経変性におけるAQP9の役割を明らかにすることを目指しています。研究内容：遺伝子改変糖尿病マウス(InsCre;Pdkflox/floxマウス)とコントロールマウスの網膜におけるAQP9の分布と発現の変化を調べた後に、両マウスでの表現型の違いを、免疫染色、TUNEL染色、血管透過性亢進、白血球接着、網膜虚血、２光子顕微鏡による生体イメージングで確認します。AQP9の神経保護効果についてはAqp9ノックアウト(KO)マウスと野生型マウスのそれぞれに高血糖誘発した後に、網膜神経節細胞数と網膜電図で評価します。血液網膜柵破綻下におけるAQP9の役割についてはマウスに抗PDGFRβ中和抗体を腹腔内投与することによって周皮細胞脱落網膜血管モデルを作成します。このモデルをAqp9KOマウスと野生型マウスでそれぞれ作成し、その表現型について上記と同様の方法で評価します。図に示します様に、私たちは世界に先駆けて２光子顕微鏡によるマウス生体網膜イメージングの系を確立しています。
期待される効果や応用分野：アクアポリンの発現と活性を調節する薬剤は多く存在することから、本研究によって糖尿病発症早期から生じる網膜神経変性におけるアクアポリン９の役割が解明されれば、糖尿病患者の網膜神経保護治療への応用が大いに期待されます。また、２光子顕微鏡によるマウス生体網膜イメージングは薬剤スクリーニングやヒトでの生体機能イメージング等への応用が期待できると思われます。